HTLV-1-associated arthropathy treated with anti-TNF-alpha agent

Human T cell leukemia virus type 1 or HTLV-1 infection is a public health problem in endemic regions like Japan, Central America or Africa. Although the majority of HTLV-1 carriers remain asymptomatic throughout their lives, some patients could develop neurological disorder, inflammatory arthropathy also called HTLV-1-associated arthropathy or T-cell malignancy, the adult T-cell leukemia/lymphoma or ATL with a very poor prognosis. Described to be very close to rheumatoid arthritis, HTLV-1-associated arthropathy patients have few or no response to the first line therapy with corticosteroids and disease modifying antirheumatic drugs or DMARDs. The use of anti-TNF-α agents in these patients is an interesting alternative but asks the question of risk of developing an adult T-Cell leukemia/lymphoma. We reported an exceptional case of a smoldering ATL patient with an HTLV-1-associated arthropathy, refractory to corticosteroid, DMARDs and rituximab therapy, treated successfully with etanercept, without progression to aggressive ATL after 5 years.     

Primary mesenteric tumor of adult T-cell leukemia/lymphoma: Report of a case

A rare case of primary mesenteric tumor of adult T-cell leukemia lymphoma (ATLL) is reported. A 64-year-old man was admitted to our hospital after the diagnosis of a palpable ileocecal tumor. Although the serologic test for human T-cell lymphotrophic virus type I (HTLV-I) antibody was positive, neither ATLL cells in the peripheral blood nor systemic lymphadenopathy were observed. At laparotomy, the tumor was histopathologically revealed to be ATLL, and wasalso found to be restricted to the mesentery. An immunohistochemical examination of the tumor tissue using a specific monoclonal antibody was positive for CD2 and CD4, and negative for CD8. Proviral genome integration in the tumor cells was found by Southern blotting using a³²p-labeled HTLV-1 probe withEcoRI andPstI digestion. Combination chemotherapy including cyclophosphamide, Adriamycin, vincristine, and prednisolone was begun postoperatively, but the patient did not respond to therapy. Up to now, only two cases of ATLL originating primarily in the abdominal cavity have been reported. These cases all demonstrate the need to consider the possibility of a primary ATLL mesenteric tumor without leukemic manifestation in the peripheral blood.     

Clinical relevance of three subtypes of primary sinonasal lymphoma characterized by immunophenotypic analysis

BACKGROUND: The purpose of this study was to investigate the clinical relevance of subtypes categorized by immunophenotypic analysis in primary sinonasal lymphomas. METHODS: Eighty patients with localized non-Hodgkin's lymphoma involving the nasal cavity and/or paranasal sinuses were divided into three subtypes on the basis of their immunohistochemical findings: (A) B-cell lymphoma (n = 19), (B) T-cell lymphoma (n = 27), and (C) natural killer (NK)/T-cell lymphoma (n = 34). The clinicopathologic profiles, immunophenotypic data, patterns of treatment failure, and survival data among the three patient groups were retrospectively compared. RESULTS: The nasal cavity was the predominant site of involvement in T-cell and NK/T-cell lymphoma, whereas sinus involvement without nasal disease was common in B-cell lymphoma. Systemic B symptoms were frequently observed in NK/T-cell lymphoma. Almost all patients with NK/T-cell lymphoma showed a strong association with the Epstein-Barr virus by in situ hybridization studies. Sixty-five patients (81%) patients achieved complete remission after initial treatment, but 36 (55%) of these subsequently experienced treatment failure. Although there were no significant differences in locoregional failure rates among the patients of the three groups, distant failure was far more common in B-cell or NK/T-cell lymphoma than in T-cell lymphoma (p =.005). Most B-cell lymphoma cases showed a predilection for sites of systemic failure in the nodal and extranodal sites below the diaphragm, such as the paraaortic lymph nodes or the gastrointestinal (GI) tract, whereas patients with NK/T-cell lymphoma showed an increased risk of systemic dissemination to the skin, testes, or GI tract, including the development of hemophagocytic syndrome. The 5-year actuarial and disease-free survival rates for all patients were 57% and 51%, respectively. Of the three subtypes of primary sinonasal lymphomas, T-cell lymphoma seemed to carry the most favorable prognosis and NK/T-cell lymphoma the worst. (The 5-year actuarial survival rate was 57% for B-cell lymphoma, 80% for T-cell lymphoma, 37% for NK/T-cell lymphoma; p =.02, log-rank.) By univariate and multivariate analyses, immunophenotype was identified as the most important prognostic factor. CONCLUSIONS: Our data indicate that the three subtypes of primary sinonasal lymphomas classified by immunohistochemical studies exhibit different clinical profiles, different patterns of failure, and different treatment outcomes. Given these observations, it is concluded that the recognition of these distinct subsets, diagnosed on the basis of immunophenotypic study, is very important and clinically relevant in predicting their potential behavior and prognosis.     

Adult T-cell lymphoma/leukemia with angioimmunoblastic T-cell lymphomalike features: Report of 11 cases

In adult T-cell lymphoma/leukemia (ATLL), the neoplastic lymphoid cells are usually medium-sized to large, often with pronounced nuclear pleomorphism compatible with the diagnosis of diffuse pleomorphic peripheral T-cell lymphoma. We describe here 11 patients with the rare morphologic variant of ATLL, angioimmunoblastic T-cell lymphoma (AILT)-like type. The examined lymph nodes showed proliferation of high endothelial venules and presence of various infiltrating inflammatory cells including plasma cells and eosinophils. The lymphoma cells were medium-to-large size with clear cytoplasm. These findings were suggestive of AILT. However, immunohistochemical features of AILT, namely, CD10 and CXCL13 expression in lymphoma cells and proliferation of CD21-positive follicular dendritic cells, were not detected. Two cases were CXCR3-positive, whereas 9 expressed CCR4, which are usually positive in ATLL. All patients were positive for antiadult T-cell leukemia/lymphoma-associated antigen, which is a specific antibody for human T-cell lymphotropic virus type-I. Southern blot analysis revealed proviral DNA integration in lymphoma cells in 9 patients. The latter was not evident in the first biopsy of 2 patients but in the second biopsy obtained within several months after the first biopsy revealed definite proviral integration. Almost all patients showed aggressive clinical course and poor survival (median survival: 5 mo). This is the first report of ATLL with AILT-like morphologic features.     

Adult T-cell leukemia/lymphoma with predominant bone involvement, initially diagnosed by its oral manifestation: a case report.

Adult T-cell leukemia/lymphoma (ATL/L) is a rare malignant neoplasm linked to human T-cell lymphotropic virus type 1 (HTLV-1). This virus has been identified in Japan, the Caribbean, and, more recently, Brazil. We report a case of ATL/L (lymphoma-type) affecting a 30-year-old Brazilian woman. She presented a painful and ulcerated lesion on her hard palate mucosa. Conventional radiographs and computed tomography revealed the involvement of several bones plus the lung and axillary lymph nodes. Histopathological and immunohistochemical analyses of oral biopsy confirmed a T-cell non-Hodgkin's lymphoma. Final diagnosis of ATL/L was made based on HTLV-1 positivity. She underwent multiple cycles of chemotherapy, which produced some improvement, but she died as a consequence of pulmonary and hepatic complications 4 months after the initial diagnosis. Besides the process of diagnosing and typing a malignant lymphoma, this article outlines the value of computed tomography and the necessity of performing HTVL-1 investigation in patients with a diagnosis of lymphoma of T-cell lineage.     

Adult T-cell leukemia/lymphoma. Clinical aspects

BACKGROUND DATA: Adult T-cell leukemia/lymphoma (ATL) is a malignant proliferation of activated CD4+ T lymphocytes. The disease is almost exclusively found in patients living in retrovirus HTLV-1 endemic areas. VIROLOGY: In ATL, monoclonal HTLV-1 provirus is integrated into atypical lymphocytes, called clover-leaf lymphocytes. The pathogenic mechanism leading to HTLV-1-induced leukemogenesis remains obscure. The disease generally occurs after a long latency period. FOUR CLINICAL SUBTYPES: The diversity of the clinical presentation has led to the classification of ATL into four subtypes: acute or prototype, lymphoma, chronic, and painless. In the acute form of ATL there is a tumor syndrome associated with paraneoplastic hypercalcemia and a high rate of opportunistic infections due to the immunodepression predominated by cellular immunity. CLINICAL COURSE: Prognosis is poor for the acute and lymphomatous forms with a median survival of 6 and 10 months respectively. Infectious episodes are frequent, often caused by Pneumocystis carinii, and require systematic prophylaxis. Screening for anguilulosis and prophylaxis is also necessary.     

Human T-cell lymphotropic virus-1-associated renal disease in Jamaican children

This report documents the clinicopathological features in two Jamaican children who presented with infective dermatitis, glomerulonephritis, renal failure and human T-cell lymphotropic virus (HTLV-1) seropositivity. Severe hypertension with hypertensive encephalopathy was the most impressive clinical feature. Histological findings from renal biopsy specimens in both cases revealed significant glomerulosclerosis with fibrosis, chronic inflammatory cell infiltrates in the interstitium, and arteriolar hypertensive changes. Membranoproliferative glomerulonephritis (MPGN) was demonstrable in case 1 and marked focal glomerulosclerosis in case 2. Case 1 developed end stage renal failure and died within 3 years of diagnosis. Case 2 remains hypertensive and in chronic renal failure. Although a causal relationship between HTLV-1 infection and renal disease cannot be proven by these two cases, it appears that renal involvement in children with HTLV-1 infection is severe, with the potential for chronic renal failure and malignant hypertension. HTLV-1 nephropathy should be suspected in children with infective dermatitis and renal disease. Received: 1 November 1999 / Revised: 21 June 2000 / Accepted: 23 June 2000     

Sinonasal lymphoma: a clinicopathologic analysis of 58 cases from the Massachusetts General Hospital.

Few large series compare lymphomas of the nasal cavity with those of the paranasal sinuses. We studied the cases of 58 patients, 34 males and 24 females, aged 7 to 92 years (mean, 57 years), who had lymphoma involving the nasal cavity or paranasal sinuses. Thirty-three patients had diffuse large B-cell lymphoma (DLBCL). Twenty-three were male and 10 were female, with an age range of 7 to 91 years (mean, 63 years); two were HIV-positive. Only 2 of 11 cases tested (one in an HIV-positive patient and one of lymphomatoid granulomatosis type) were Epstein-Barr virus (EBV)-positive. Thirty (91%) involved paranasal sinuses, 10 with nasal involvement, whereas three cases had nasal, but not sinus, involvement. At last follow-up, 16 (67%) were free of disease 7 to 169 months later (mean, 65 months), and 8 (33%) had died of disease 2 to 166 months later (mean, 45 months). Seventeen patients had nasal-type natural killer (NK)/T-cell lymphoma. There were 10 women and 7 men, aged 27 to 78 years (mean, 48 years). Thirteen of 14 were EBV-positive. Sixteen patients had nasal involvement, eight with sinus involvement. Eleven (73%) of 15 were alive and well 6 to 321 months later (mean, 139 months), three (20%) died of lymphoma 1, 11, and 12 months later, and one (7%) is alive with disease. There was one case each of marginal zone B-cell lymphoma, Burkitt's lymphoma, Burkitt-like lymphoma, peripheral T-cell lymphoma of unspecified type, and adult T-cell lymphoma/leukemia. In an additional three cases, the lymphomas were composed predominantly of large cells, but no immunophenotyping could be performed for subclassification. In 19 cases (17 DLBCLs, 1 Burkitt-like lymphoma, and 1 lymphoma of uncertain lineage), presenting symptoms included complaints related to the eyes. In 16 cases (13 DLBCLs, 1 Burkitt-like lymphoma, 1 nasal NK/T-cell lymphoma, and 1 lymphoma of uncertain lineage), the orbit was invaded by lymphoma. In our series, the most common lymphoma to arise in the sinonasal area is DLBCL, followed by nasal NK/T-cell lymphoma. Comparison of these two types of lymphoma showed that lymphomas involving sinuses without nasal involvement were predominantly DLBCLs (20 of 21), whereas nasal cavity lymphomas without sinus involvement were usually NK/T-cell type (8 of 11) (p = 0.000125). Compared with patients with DLBCL, patients with nasal NK/T-cell lymphoma were overall younger, with a lower male-to-female ratio. Lymphomas of B-cell lineage were more likely to be associated with symptoms related to the eyes (p < 0.0005) and to have extension to the orbit (p < 0.01) than were lymphomas of T- or NK-cell lineage. In contrast to results of Asian studies in which nasal NK/T-cell lymphoma has a very poor prognosis, our nasal NK/T-cell lymphomas had an outcome similar to that of DLBCL.     

Post Transplant T-Cell Lymphoma: A Case Series of Four Patients from a Single Unit and Review of the Literature

Post-transplant lymphoproliferative disorders (PTLDs) occur in approximately 1% of renal graft recipients. Of these, up to 15 percent are of the T-cell type. In this study, we present four cases of T-cell lymphoma from our renal transplant population, each of whom presented with non-specific symptoms, pancytopenia and/or liver dysfunction, with no obvious lymphadenopathy. They were all diagnosed with rare subsets of T-cell PTLD that included hepato-splenic T-cell lymphoma and anaplastic large cell lymphoma (ALCL). At the time of presentation, the patients were too ill for treatment to be initiated and succumbed to their illness. Increased awareness of this condition may allow for earlier diagnosis and improve its prognosis.     

Primary malignant lymphoma in the sphenoid sinus with orbital apex syndrome; a case report]

Only 2.0-6.8% of extranodal malignant lymphomas are found in the nasal region and paranasal sinuses. Primary malignant lymphoma of the paranasal sinuses usually occurs in the maxillary or ethmoid sinuses, and is very rare in the sphenoid sinus. Here we report a rare case of primary malignant lymphoma of the sphenoid sinus that was found accompanying orbital apex syndrome. The patient's progressively deteriorating neurological condition was improved after surgery via the transsphenoidal approach. A 52-year-old man was admitted with reduced left visual acuity, diplopia, and retroorbital pain. CT showed an isodense mass in the sphenoid sinus with slight enhancement, and MRI showed that the lesion was slightly hypointense on T1-weighted images, hypointense on T2-weighted images, and slightly enhanced by Gd-DTPA. On January 19, 1989, the patient suddenly became blind. An operation via the transsphenoidal approach was done as an emergency procedure to decompress the sphenoid sinus and the left optic canal. The histological diagnosis was non-Hodgkin's lymphoma of the diffuse large cell type (B cell lymphoma). Malignant lymphoma in the paranasal sinuses is usually biopsied and treated by chemotherapy and/or radiotherapy without surgical resection. In this rare case, an operation via the transsphenoidal approach was effective in improving the patient's visual acuity.     

Primary T-cell lymphoma with myelopathy associated with HTLV-1

The case of a patient who had myelopathy associated with human T-cell lymphotropic virus Type 1 (HTLV-1) for 10 years and developed a T-cell lymphoma in the cerebellum is reported. The relationship between myelopathy associated with HTLV-1 and primary T-cell lymphoma is discussed.     

Sézary Syndrome

Sézary syndrome (SS), a type of cutaneous T-cell lymphoma with a poor prognosis, is characterized by erythroderma and leukemic involvement. Because of the rarity of SS and difficulty in diagnosis, data on this aggressive malignancy are scarce. In this review, the diagnosis and pathology of SS are summarized and an update is provided, highlighting microscopic features and novel molecular findings. The diagnostic challenge of SS is described, with an emphasis on the differential diagnosis of erythroderma and key points in distinguishing SS from other cutaneous T-cell malignancies. Finally, the prognosis is discussed, focusing on large, recent studies of SS patients.     

Extranodal NK/T-cell lymphoma presenting as a pituitary mass. Case report and review of the literature

Primary pituitary lymphomas (PPLs) are rare tumors of the central nervous system, and most are of B-cell origin. Extranodal NK/T-cell lymphomas are uncommon neoplasms that are highly aggressive and show a strong association with Epstein-Barr virus. They most commonly affect the nasal cavity and paranasal sinuses; manifestation as a primary pituitary tumor has never been described. The authors report a case of NK/T-cell lymphoma of the pituitary gland and review 17 cases of PPL from the literature. All patients had been evaluated at presentation for clinical, neuroimaging, and histopathological findings. Patients who had systemic lymphoma with secondary involvement of the pituitary gland were excluded. The mean patient age was 55.5 years (range 26-86 years); the male/female ratio was 13:5. The most common presentation was pituitary insufficiency (72%), followed by headache (56%), diplopia (39%), visual loss (28%), and fever (22%). Thirteen patients (72%) exhibited anterior hypopituitarism and seven (39%) had diabetes insipidus at presentation. Magnetic resonance imaging demonstrated enhancing parasellar masses with diffuse enlargement of the pituitary gland (94%), suprasellar extension (44%), cavernous sinus extension (39%), and stalk thickening (22%). Thirteen patients (72%) had B-cell lymphoma, four (22%) had T-cell lymphoma, and one (6%) had NK/T-cell lymphoma. Primary pituitary lymphomas are rare entities with a range of clinical presentations and neuroimaging findings that are unique from those of patients who present with pituitary adenomas. The pathological entity of NK/T-cell lymphoma is distinct, and its course is very aggressive with a poor prognosis.     

肠道NK／T细胞淋巴瘤4例诊治分析

目的：探讨肠道NK／T细胞淋巴瘤的临床特点、诊断及治疗。方法：回顾性分析4例肠道NK／T细胞淋巴瘤的临床资料,对其发病特点、临床表现、实验室检查、诊断和治疗方法进行总结分析。结果：3例为小肠NK／T细胞淋巴瘤,CD45RO（＋）,cD3（＋）,CD56（＋）,CD20（-）,TIA（-）。1例为结肠NI/T细胞淋巴瘤,CD45RO（＋）,CD3（＋）,CD56（＋）,CD20（-）,TIA（＋）。4例患者术后分别存活61、58、14、7d。结论：肠道NK／T细胞淋巴瘤确诊需依赖术后病理组织学及免疫组织化学检查,早期诊断、尽早实施合理的治疗是降低死亡率的关键。     

CD30-Negative Cutaneous T-Cell Lymphomas Other than Mycosis Fungoides

Cutaneous T-cell lymphomas (CTCLs), other than mycosis fungoides/Sézary syndrome and the group of cutaneous CD30⁺ lymphoproliferative disorders, are rare. These include subcutaneous panniculitis–like T-cell lymphoma (SPTCL); extranodal natural killer/T-cell lymphoma, nasal type; primary cutaneous peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS); and rare subtypes of PTCL, NOS. Apart from SPTCL and primary cutaneous CD4-positive small-medium pleomorphic T-cell lymphoma, these lymphomas have in common aggressive clinical behavior and poor prognosis. Differentiation between these different types of CTCL may be difficult and requires integration of histopathologic findings with clinical data and the results of phenotypic and often molecular genetic studies.     

Primary gastric T-cell lymphoma without human T-lymphotropic virus type 1: report of a case

Although primary gastric malignant lymphoma accounts for slightly more than 10% of all lymphomas at extranodular sites, it is relatively rare clinically, representing only 1% of all malignant diseases of the stomach. In addition, most such diseases tend to be B-cell lymphoma, while T-cell lymphoma is extremely rare. We encountered a patient with primary gastric T-cell malignant lymphoma who, although demonstrating a very rare phenomenon, was negative for antihuman T-lymphotropic virus type 1 antibody. A 73-year-old man was admitted to the hospital with the chief complaint of upper abdominal pain. The primary lesion was a type 3 tumor located at the cardia to the posterior wall of the upper body of the stomach, which had invaded the tail of the pancreas and a part of the transverse colon. A total gastrectomy, pancreatosplenectomy, and partial resection of the transverse colon were performed. The surgical section contained a giant ulcerative lesion with its bank cleaved, and a histological examination revealed a diffuse, small cell (Lymphoma Study Group classification) malignant lymphoma. An immunohistochemical analysis of the surgical specimen was positive for LCA/CD45, UCLH-1/CD45RO, and Leu-4/CD3, and negative for L-26/CD20, and it was diagnosed to be primary gastric T-cell malignant lymphoma. Received: June 28, 2001 / Accepted: November 20, 2001     

Primary T-cell lymphoma of the thyroid

BACKGROUND: The routine use of immunocytochemical analysis has led to the recognition that many thyroid neoplasms previously diagnosed as anaplastic or small cell carcinomas are actually lymphomas of the thyroid. The great majority are B-cell lymphomas which can be associated with Hashimoto's thyroiditis. In spite of this, thyroid lymphomas are still not commonly recognized as a significant part of thyroid differential diagnosis. METHODS: A rare case of a primary T-cell lymphoma of the thyroid gland is presented along with general clinical history and physical findings which should make the practitioner suspicious of a thyroid lymphoma. The usefulness of radiology scans and fine-needle aspiration are discussed. RESULTS: Both prognosis and treatment options are very different for thyroid lymphomas and anaplastic carcinoma. CONCLUSIONS: Cyclophosphamide/adriamycin/vincristine/prednisolone chemotherapy/radiotherapy regimens have proven to be very effective for most thyroid lymphomas.     

Primary spinal epidural mantle cell lymphoma: case report

OBJECTIVE AND IMPORTANCE: Mantle cell lymphoma is a distinct clinicopathological type of non-Hodgkin's lymphoma that often presents at an advanced stage, with systemic spread. Spinal involvement is uncommon and generally occurs as part of advanced disease or generalized relapses. Primary spinal epidural lymphoma is a rare initial manifestation of non-Hodgkin's lymphoma, and mantle cell lymphoma with initial presentation in the spinal epidural space is extremely rare, having been previously reported in only two cases. CLINICAL PRESENTATION: We report a case of a 71-year-old man who presented with increasing weakness and numbness of the legs. Magnetic resonance imaging revealed a spinal epidural mass in the lumbosacral region. INTERVENTION: The patient underwent a partial L4 and L5-S1 laminectomy, with incomplete resection of the mass for spinal decompression and tissue diagnosis. Mantle cell lymphoma was diagnosed in the pathological examination. CONCLUSION: After radiotherapy, the disease recurred with a soft-tissue mass in the anterior maxillary area of the face. The patient underwent restaging and was treated with chemotherapy, with only a partial response. Mantle cell lymphoma with primary spinal epidural presentation is rare. This diagnosis can be established and other causes of spinal cord compression can be ruled out by obtaining tissue for proper histopathological examinations. Because of its aggressive behavior and poor prognosis, mantle cell lymphoma should be treated using a combined-modality approach.     

Rare oral cavity presentation of a B-cell lymphoblastic lymphoma. A case report and review of the literature.

Lymphoblastic lymphoma is an uncommon malignancy, with most cases showing a T-cell phenotype and presenting as a mediastinal mass. By contrast, B-cell lymphoblastic lymphoma/leukemia is a rare high-grade malignancy that comprises approximately 10% of all lymphoblastic lymphomas. Lymphomas of the oral cavity are rare and typically present as intraosseous lesions that are most commonly diffuse large B-cell type. Here we present what we believe is the first B-cell lymphoblastic lymphoma initially presenting in the oral cavity. The case involves a 46-year-old white woman who presented with a mass in the right mandible. This report discusses this rare malignancy, including clinical presentation, histopathologic features, immunologic profile, treatment, and prognosis. This case emphasizes the importance of recognizing rare entities that may present in the oral cavity and the impact of the disease and its management.     

Human T-cell leukemia virus type 1 infection worsens prognosis of hepatitis C virus-related living donor liver transplantation

Severe and life-threatening donor-transmitted human T-cell leukemia virus type 1 (HTLV-1) infections after solid organ transplantation have been reported. However, in HTLV-1-infected recipients, graft and patient survival were not fully evaluated. A total of 140 patients underwent living donor liver transplantation (LDLT). Of these, 47 of 126 adult recipients showed indications of hepatitis C virus (HCV)-related liver disease. The HTLV-1 prevalence rate was 10 of 140 recipients (7.14%) and three of 140 donors (0.02%). In HCV-related LDLT, graft and patient survival was worsened by HTLV-1 infection in recipients (seven cases). The 1-, 3-, and 5-year survival rates in the HCV/HTLV-1-co-infected group were 67%, 32%, and 15%, respectively, and the corresponding rates in the HCV-mono-infected group were 80%, 67%, and 67%, respectively. Only the 5-year survival rates were statistically significant (P=0.04, log-rank method). HTLV-1 infection in recipients is also an important factor in predicting survival in HTLV-1 endemic areas.