HTLV-I induced extranodal lymphomas.

HTLV-I induced not only nodal but also primary extranodal lymphomas. In this report we describe 12 patients with HTLV-I induced extranodal T-cell lymphoma collected from the literature and our institute experience. There were 5 males and 7 female patients of middle age positive for HTLV-I antibody. The sites of primary tumor were gastrointestinal, Waldeyer's ring, skin, facial sinuses, and the pleura. All of these were histologically diffuse lymphomas and most of them were found to be a helper/inducer T-cell phenotype, showing integration of HTLV-I proviral DNA. Late leukemic changes and skin infiltration often occurred, but hypercalcemia was rare. Survival time varied from 4 to 35 months, and late organ infiltrations were common. These HTLV-I induced extranodal lymphomas were compared with HTLV-I unrelated extranodal lymphomas or HTLV-I induced nodal lymphomas (lymphoma type ATL). Between 1981 and 1990, we had 110 ATL patients and of these, 5 (4.6%) were HTLV-I induced primary extranodal lymphomas. The frequency of HTLV-I induced extranodal lymphoma might be much higher than expected because until now attention has not been paid to this entity. From the present review, it is suggested that HTLV-I could cause primary extranodal lymphoma which may have some different characteristics from other types of lymphoma. Therefore, patients with T-cell extranodal lymphomas should be investigated further for the presence of HTLV-I antibody and the tumor cells should be examined for the integration of HTLV-I proviral DNA using Southern blot analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary extranodal lymphomas of gastrointestinal localizations

This study is aimed at comparison of patients with extranodal lymphomas based on pathohistological findings differences (MALT vs non-MALT) as well as regarding gastric and non-gastric localization, and determining the significance of clinical-laboratory parameters with respect to therapeutic response and length of survival. A total of 56 patients with extranodal non-Hodgkin's lymphomas of the gastrointestinal tract were evaluated over a 5-yr period. Regarding the localization of the disease, the stomach was most frequently affected, 39 patients (70%); followed by small and large intestines, 17 patients. As for the pathohistological findings, MALT lymphoma accounted for 70%, DLBCL 25%, while other subtypes accounted for 5%. Patients' distribution was analyzed according to CS based on both Ann Arbor and Lugano systems; however, the difference obtained between the groups was not statistically significant in both staging types of patients. Statistically significant difference in patients' distribution was not found with respect to IPI index, bone marrow infiltration, anemia, hypoalbuminemia, or histological subtype and localization. Difference in survival between patients according to the pathohistological type was not statistically significant also according to the type of the affected gastrointestinal tract organ. Statistical significance of difference according to survival probability was obtained based on age (survival is longer in patients over 55 yr of age); according to CS and according to Ann Arbor and Lugano classifications (the patients with lower CS live significantly longer); according to IPI index (the survival is significantly longer in patients with lower probability: IPI-0,1, and 2), as well as patients free of bone marrow infiltration whose survival is also significantly longer.     

淋巴结外淋巴瘤的误诊分析与对策

目的　对结外淋巴瘤的误诊原因分析并提出相应的防止对策。方法　自 1980年 1月至 2 0 0 0年 7月 ,对收治非霍奇氏淋巴瘤 85例患者进行回顾性分析。结果　 85例非霍奇氏淋巴瘤中结外淋巴瘤 5 0例 ( 5 8.5 %) ,误诊 30例 ,误诊率高达 6 0 %。 30例中发生于消化道者最多 ,共 11例 ( 36 .6 %) ,其次为鼻及咽部组织 ,共 7例 ( 2 3.3%) ,其它部位少见共12例 ( 4 0 %)。结论　结外淋巴瘤误诊发生于消化道、鼻及咽部组织为多。但可发生于任何器官组织 ,其临床表现无特征性 ,诊断困难 ,易发生误诊。临床医师必须具有多学科横向知识 ,加强对结外淋巴瘤的认识 ,并尽快进行病理学检查。     

Long‐term outcome in localized extranodal mucosa‐associated lymphoid tissue lymphomas treated with radiotherapy

BACKGROUND:

This study was conducted to evaluate the long‐term outcomes in patients with stage IE and IIE mucosa‐associated lymphoid tissue (MALT) lymphomas treated with involved field radiotherapy (RT).

METHODS:

Between 1989 and 2004, 192 patients with stage I and II MALT lymphomas were treated. The report focuses on 167 patients who received RT. The median age of patients was 58 years with a female predominance (2:1). Presenting sites were as follows: orbital adnexa in 71 patients, salivary glands in 28 patients, stomach in 25 patients, thyroid in 21 patients, and other sites in 22 patients. The median dose to nonorbital sites was 30 grays (Gy) (range, 17.5‐35 Gy) and was 25 Gy for the orbit (range, 25‐35 Gy). The median follow‐up was 7.4 years (range, 0.67‐16.20 years).

RESULTS:

Complete response and complete response, unconfirmed (CR/CRu) was noted in 166 (99%) patients. The 10‐year recurrence‐free rate (RFR) was 76%, the disease‐free survival (DFS) rate was 68%, the overall survival (OS) rate was 87%, and the cause‐specific survival rate was 98%. According to presenting site, the 10‐year RFR was 95% for thyroid, 92% for stomach, 68% for salivary glands, and 67% for orbit. Patients with thyroid and gastric MALTs had better outcome compared with patients with MALTs diagnosed at other sites (P = .004). Among those patients who achieved CR, 19% developed disease recurrence (n = 31), chiefly in distant sites or untreated contralateral‐paired organs. At the time of disease recurrence, 7 patients (23%) had transformed to diffuse large B‐cell lymphoma, 2 of whom died of lymphoma. The 5‐year OS rate after treatment failure was 83%.

CONCLUSIONS:

Patients with localized MALT lymphomas are reported to have excellent clinical outcome after moderate‐dose RT, and some are likely cured. In the current study, thyroid and gastric MALTs were found to have significantly less risk of distant recurrence. Despite disease recurrence, the overall survival remains excellent in these patients. Cancer 2010. © 2010 American Cancer Society.     

Non-Hodgkin's lymphomas of head and neck extranodal sites

The initial staging, therapy and course of 156 patients with non-Hodgkin's lymphomas of head and neck extranodal sites were analyzed to determine whether they have a natural history which differs from primary nodal disease. The sites involved were: Waldeyer's ring-103 patients (tonsil-60, nasopharynx-25, base of tongue-18), and extralymphatic sites-53 patients (salivary gland-20, paranasal sinus-20, oral cavity-10, and larynx-3). Seventy-six percent had unfavorable histologies and 24% had favorable histologies. Fifty-three percent had pathologic Stages I-II and 47% had Stages III-IV. The 5-year survival was influenced by primary sites: salivary gland-61%, oral cavity-57%, tonsil-49%, base of tongue-47%, nasopharynx-36% and paranasal sinus-12%. The 5-year survival was also influenced by histology: unfavorable histologies-39%, favorable histologies-69%. The Ann Arbor staging system was more useful than TNM for determining outcome. For patients with Stage I-II unfavorable histologies treated with radiation alone, the 5-year survival was: involved field-24%, extended field-42%, total lymphoid irradiation-52%. The majority of patients who failed did so in extranodal sites. Forty-one patients with advanced disease received a variety of chemotherapy regimens as the sole treatment. There was a high percentage of CNS recurrence with paranasal sinus lymphoma, and CNS prophylaxis may be necessary. For head and neck extranodal lymphomas, limited radiation is inadequate, and combined modality programs should be considered.     

Clinical course of early extranodal non-Hodgkin's lymphomas.

The subsequent sites of relapse following local X-ray therapy treatment of early stage non-Hodgkin's lymphoma were analyzed. The short interval to recurrence, the involvement of noncontiguous sites, and the rapid progression to death all suggest that seemingly early extranodal non-Hodgkin's lymphoma often is disseminated at diagnosis and that local treatment alone is ineffective. The analysis of sites of first relapse suggests that extended field treatment such as total nodal irradiation would benefit only a minority of these patients but would be superior to a radiation technique covering only the adjacent lymph node regions. While immediate contiguity of lymph node involvement was often seen with extranodal presentations, the more common pattern of relapse in bone marrow, liver, lung, stomach, and extranodal sites, indicates the need for an effective systemic therapy.     

Clinicopathological features of extranodal lymphomas: Kuwait experience

A total of 935 patients with extranodal non-Hodgkin lymphoma (NHL) diagnosed in the period between January 1985 and December 2000 in Kuwait Cancer Center, serving the whole population of Kuwait, were used to describe the clinicopathological and epidemiological features of extranodal lymphomas in Kuwait. Extranodal lymphomas accounted for 45% of all NHL observed during this time. All NHL cases from Kuwait Cancer registry were analyzed and pathologically reclassified using the latest WHO (2000) classification. The most common lymphoma observed was diffuse large B-cell lymphoma (58.60%) followed by Burkitt s lymphoma (BL) (3.80%). In the pediatric group, BL comprises more than two thirds of all patients (77.20%). The most common extranodal sites were stomach (19.70%) and skin (17.80%) in the adult group, large intestine (29.80%) and small intestine (19.30%) in the pediatric age group. The majority (73.40%) of adult extranodal lymphomas was in stage IE-IIE and had a very good prognosis. On the contrary, the majority of pediatric extranodal lymphomas were found to be in stage III and IV. Variations in treatment policies (single agent or combined chemotherapy, radiotherapy, combined modality treatment) adopted and changed during the time period of 16 years of this retrospective study were documented.     

Head and neck extranodal non-Hodgkin's lymphomas in Indian patients

Though radiotherapy has traditionally been the treatment of the choice for the patients with localised extranodal lymphomas of the head and neck areas, its adequacy as the sole modality of treatment has come to be questioned. The disease is shown to relapse in other distant extranodal sites especially the gastrointestinal tract. The addition of systemic chemotherapy has been suggested. Fifty-five patients with localised head and neck extranodal lymphomas were treated at the Tata Memorial Hospital during the period 1976-1982, 35 with radiation therapy alone and 20 with combination therapy. The total survival at 5 years was 65% for patients treated with radiation alone and 85% for those treated with combination therapy. The 5 year disease-free survival dropped to 45% for the former group but was 74% for the latter group. This difference was statistically significant (p less than 0.01). We infer that localised extranodal lymphomas be regarded as a systemic disease and be treated by a multimodal approach.     

Immunohistochemical detection of high endothelial venules in extranodal B-cell lymphomas

The hypothesis that extranodal malignant lymphomas, such as thyroid, stomach, rectum, ileum and uterus, eventuate from long-standing inflammation is essentially tested using a monoclonal antibody (HECA-452) to an endothelial-associated antigen selectively expressed by the high endothelim of post-capillary venules (HEVs) normally present in lymph nodes, tonsils and mucosa-associated lymphoid tissues. The presence of HEVs was examined on freshly prepared specimens from 16 cases of extranodal lymphoma of the B-cell type (eight thyroid, three stomach, two rectum, one ileum, one uterus, one tonsil). Control cases included reactive lymph nodes, nodal lymphoma of T-cell type, epithelial neoplasia, bone and soft tissue sarcomas, glioblastoma, thyroid affected by chronic lymphocytic thyroiditis (CLTH), thyrotoxicosis (Grave's disease) or nodular goiter, and salivary gland affected by Sjogren's syndrome (SS). HECA+ HEVs were present in reactive lymph nodes, nodal lymphoma, and all but one case of thyroid, all cases of stomach and all cases of rectal lymphoma, together with all CLTH and SS, both known to be autoimmune diseases. No thyroid, ileal or uterine lymphoma cases had any HECA positive venules. HECA+ venules were present in extranodal lymphomas, either adjoining the lymphoid follicles observed in several cases or in the diffusely proliferating tumor cells. Previous studies have shown that HEVs appeared in association with long-standing inflammation. The present study therefore, suggested that extranodal lymphomas of the thyroid, stomach and rectum evolve in long-standing inflammation, forming HEVs.     

Multifocal extranodal lymphomas: an expression of homing phenomenon.

The present study analyses 27 patients with primary lymphoma involving multiple extranodal sites. Eight patients were found to have multiple extranodal involvement at presentation while in 19 patients, relapse of disease was noticed at a different extranodal site without any other systemic spread. Malignant lymphomas of Waldeyer's ring were frequently associated with involvement of gastrointestinal, gonadal or cutaneous lesion. Primary gonadal lymphoma also showed a high incidence of cutaneous, pleura and bone involvement. The homing pattern of mucosa-associated lymphoid cells explains the multifocal extranodal lymphomas with site-specific tropism.     

Clinicopathologic features and prognostic factors of primary extranodal non-Hodgkin's lymphomas in Turkey

Clinical, histopathologic, and prognostic features of 114 patients with primary extranodal non-Hodgkin's lymphoma were evaluated. Median age of the patients was 48 (range, 15-76) and the ratio of male/female was 55/59. Thirty-seven patients had stage 1, 55 patients stage II, 6 patients stage III, and 16 patients stage IV. The most common sites of primary extranodal non-Hodgkin's lymphoma were the gastrointestinal (GI) tract and head-neck region. Stomach (66%) and tonsils (33%) were the most frequently involved organ in GI tract and head-neck region, respectively. Eighty percent of patients had intermediate or high-grade lymphomas, 20% had low-grade subtypes. Complete remission was achieved in 83% of all patients with chemotherapy +/- radiotherapy +/- surgery. Overall and disease-free survival at 5 years were 63% and 59%, respectively. In conclusion, clinical and histopathologic characteristics and prognosis of our cases with primary extranodal non-Hodgkin's lymphoma were usually similar to those of the cases in Western countries with some differences in the incidence of some specific primary extranodal non-Hodgkin's lymphomas and in the histopathologic subtypes.     

Primary extranodal lymphomas of Waldeyer's ring, stage IE and IIE

We reviewed 45 cases of Waldeyer's ring lymphomas (25 stage IE, 20 IIE): 73% had high-grade histology according to Kiel's classification. Fourteen patients received radiotherapy alone and 31 chemotherapy, combined with radiotherapy in 28. Complete remission rate was 95% and relapse rate 32%. At 8 years overall disease-related survival (DRS) and event-free survival (EFS) were 69% and 57% respectively. Combined treatment provided both significantly better DRS (82% vs 42%) and EFS (76% vs 25%) than radiotherapy alone. Most of the patients with high-grade histology (26/33) received the combined treatment and this subgroup achieved a long-term EFS of 78%. Both DRS and EFS were also significantly longer in patients under 60. At multivariate analysis favorable prognostic factors were lower age for DRS and combined treatment for EFS.     

Radiation therapy for localized low-grade non-Hodgkin's lymphomas

The most common low grade B-cell non-Hodgkin's lymphomas are follicular lymphomas, and extranodal marginal zone lymphomas, also known as mucosa-associated lymphoid tissue (MALT) lymphomas. Localized presentations of follicular lymphoma occur in 20-30% of cases, while for MALT lymphomas, stage I-II disease presentations occur in 70-90%. These are radiation-sensitive lymphomas. Following moderate dose local radiation treatment (30-35 Gy) for these stage I and II low grade lymphomas, the clinical results indicate long-term local control and possible cure. While local control is achieved with minimal morbidity with involved-field radiation therapy, a significant proportion of patients relapse with systemic disease outside of radiation fields. For follicular lymphoma, this occurs in approximately 50% of patients after 15 years, and for non-gastric MALT lymphoma, 30-40% after 10 years. Although patients with relapsed systemic disease are not curable with chemotherapy, the disease often behaves in an indolent fashion and prolonged survival is observed. For gastric MALT lymphomas, radiation therapy is indicated in patients whose lymphoma did not respond to Helicobacter pylori eradication therapy, or in gastric lymphoma not related to this microorganism. The subject of causative agents responsible for non-gastric MALT lymphomas is under active study and the identification of putative microorganisms will lead to improved treatment strategies for these unusual lymphomas, similar to the success in gastric lymphomas over the last decade.     

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.     

Unusual presentation of extranodal peripheral T-cell lymphomas with multiple paraneoplastic features.

Three patients with extranodal peripheral T-cell lymphoma and a distinctive clinical presentation are described. They had acute onset of fever, weight loss, progressive liver failure, bleeding diathesis, pancytopenia, and myelodysplastic changes in the bone marrow. Each patient had one or more paraneoplastic complications: severe rhabdomyolysis with myoglobinuria and secondary renal failure, cutaneous vasculitis, gluten-sensitive enteropathy, polyserositis, and increased macrophages with hemophagocytic activity. They did not have peripheral lymphadenopathy. The complex clinical presentations simulated collagen vascular disorders, systemic infections, or severe liver disease rather than a malignant lymphoma. Routine histologic studies revealed a small population of lymphoma cells in the bone marrow, spleen, and liver. Immunophenotyping studies demonstrated their T-cell phenotype, and cytogenetic analysis showed the clonality in Patients 1 and 2; clonal T-cell receptor gene rearrangement was found in Patients 2 and 3. These studies should be considered in the evaluation of patients with constitutional symptoms, liver failure, coagulopathy, and pancytopenia even in the absence of peripheral lymphadenopathy.     

Bronchus-associated lymphoid tissue lymphomas: an update of a rare extranodal maltoma

Mucosa-associated lymphoid tissue (MALT) lymphomas were first described by Isaacson and Wright in 1983 in a small series of patients with low-grade B-cell gastrointestinal lymphomas. Although MALT lymphomas occur most frequently in the stomach, they have also been described in various non-gastrointestinal sites, such as the salivary gland, conjunctiva, thyroid, orbit, lung, breast, kidney, skin, liver, uterus, and prostate. The risk of a diagnostic dilemma is reduced by the favorable prognosis of this low-grade lymphoma and its tendency to remain localized to the primary site for a long time. On therapeutic grounds, in contrast to nodal lymphomas, low-grade MALT lymphomas also respond favorably to local treatments, such as surgery and/or local radiation therapy. The outcome and prognosis of low-grade MALT lymphomas are more favorable than those for other extranodal lymphomas. The purpose of this review is to point out the state of the art regarding bronchus-associated lymphoid tissues lymphomas in terms of etiology, pathogenesis, clinics, and therapeutics, including our single-center experience of 23 cases.