Low-grade gliomas of chronic epilepsy: A distinct clinical and pathological entity

The authors present a summary of their recent experience regarding the management of patients with a variety of low-grade gliomas found during the evaluation for chronic epilepsy. These tumors are notable because the long-term patient outcome in this population is significantly better than the anticipated results of patients with the same tumors who do not have chronic epilepsy. Based on the long history of preoperative seizures (median 14 years), the frequent cortical location, and the absence of tumor recurrence or anaplastic transformation and the lack of mortality in this population, low-grade gliomas of chronic epilepsy appear to define a specific pathological entity that separates them from other histologically similar low-grade gliomas. Low-grade gliomas of chronic epilepsy also are notable for the absence of morphological features that characterize with dysembryoplastic neuroepithelial tumors (DNTs). Our evidence suggests that low-grade gliomas of chronic epilepsy should be recognized as a distinct pathological entity.     

Blastic CD4 NK cell leukemia/lymphoma: a distinct clinical entity

We report the findings of three new cases of a distinct clinicopathologic natural killer (NK) cell malignancy characterized by cutaneous, nodal and bone marrow infiltration by CD3-CD4+CD56+ NK blastic cells. Tumor cells were detected in bone marrow and in peripheral blood smears and showed finely distributed nuclear chromatin with nucleoli and a moderate amount of cytoplasm. Epstein-Barr virus (EBV) DNA was negative in the two tested cases. The immunophenotypes determined by flow cytometry were identical concerning mCD3-cytCD3-CD4+weakCD56+ HLA-DR+. The TCR was in germline configuration in the two cases tested. NK cell activity was demonstrated only in one out of the two cases tested. The negative reactions with alpha-naphthyl-acetate-esterase (ANAE), CD11b and CD14 strongly suggested that the tumor cells were not of the monocytic lineage.     

'Aggressive' angiomyxoma: a distinct clinical entity.

AIM: An aggressive angiomyxoma is a mesenchymal tumour arising from connective tissues of the perineum or lower pelvis. They cause very little symptoms despite their large size. METHODS: All patients with a diagnosis of aggressive angiomyxoma were studied retrospectively from a prospective database at the Royal Marsden Hospital between January 1990 and July 2001. RESULTS: There were seven female patients with a diagnosis of aggressive angiomyxoma. Sites of involvement included the soft tissues of the perineum (n=4), vulva (n=2) and inguinal region (n=1). The common presenting feature was a mass. The size of the tumour was larger than 10 cm in three patients. Two patients had an intracapsular excision, two had marginal resection and in two patients wide excision was done. Four patients developed recurrent tumour with an interval ranging from 6 months to 97 months. Recurrence was not observed in the two patients after wide excision at intervals of 8 and 13 months. CONCLUSION: The tumour is aggressive in that it has a propensity for recurrence but usually in the long term. Operation can cure patients with aggressive angiomyxoma, but may result in significant morbidity due to the large size of the tumour at presentation and its frequent occurrence in the lower pelvis and perineum with proximity to genitourinary and anorectal structures. A period of watchful waiting to assess growth rate may be the most appropriate course in most patients. Surgery whenever offered for symptom control should be done with minimal morbidity.     

State-of-the-art therapeutics: marginal-zone lymphoma.

Marginal-zone lymphomas comprise the mucosa-associated lymphoid tissue (MALT) type (extranodal marginal-zone lymphoma [EMZL]), the nodal marginal zone B-cell lymphoma (NMZL) and the splenic MZL (SMZL). EMZL is relatively common, whereas the remaining two entities are relatively rare disorders. EMZL, especially in its gastric localization, is the most studied MZL, and there are many data both on the underlying genetic lesions and on the role of infectious agents. These data have determined unique approach among all other lymphoma subtypes: the possibility of treating a subset of patients with antibiotics alone as first line of treatment. Indeed, there is compelling evidence that histologic regressions can be achieved in most gastric MALT lymphomas by eradicating Helicobacter pylori infection. However, molecular follow-up studies showed the persistence of the malignant clone in half of the cases in histologic remission after antibiotic treatment and transient, either histologic or molecular, relapses have been reported, too. Hence, a careful long-term follow-up is mandatory after antibiotic treatment. Radiotherapy, chemotherapy, anti-CD20 monoclonal antibodies are effective alternative therapies. The precise role of surgical resection should be redefined in view of the encouraging results of conservative approaches. Differently from EMZL, both SMLZ and NMZL often present with disseminated disease at diagnosis. The therapeutic approach comprises splenectomy, for SMZL, and chemotherapy, but with no consensus about the best treatment. This review addresses the current knowledge on the clinical features and therapeutic approaches for the individual MZLs.     

Human herpesvirus 8-negative malignant effusion lymphoma: a distinct clinical entity and successful treatment with rituximab

We describe 2 elderly patients with Human herpesvirus 8 (HHV-8)/Kaposi sarcoma herpes virus negative malignant effusion lymphoma showing pan-B-cell immunophenotyping markers and successfully treated with a chimeric anti-CD20 IgG1 monoclonal antibody, rituximab. A 90-year-old man and an 87-year-old woman were hospitalized because of pleural effusions. They were diagnosed as having malignant effusion lymphoma on the basis of cytologic and flow cytometric findings of effusions, revealing involvement of atypical lymphoid cells and expression of CD19 and CD20. The former case was intolerant of chemotherapy because of toxicity. Using the conventional dose of rituximab, they showed neither intolerance nor adverse effects and their pleural effusions decreased immediately. Any sign of disease progression was not noted in either of the patients. They were negative for a HHV-8 infection and had no history of pyothorax. This type of lymphoma was not compatible with primary effusion lymphoma (PEL) defined by World Health Organization Classification of Tumors or pyothorax-associated lymphoma. We diagnosed these patients as having "HHV-8 negative malignant effusion lymphoma". HHV-8 negative malignant effusion lymphoma may be a new clinicopathologic and biologic entity. Because most of the cases were positive for pan-B-cell markers, rituximab may be a promising agent for the treatment.     

Primary effusion lymphoma (PEL) in HIV-negative patients--a distinct clinical entity

Primary effusion lymphoma (PEL) is a recently described rare type of non-Hodgkin's lymphoma occurring almost exclusively in HIV infected people. Human herpesvirus 8 (HHV-8), has been linked with PEL, and a causative relationship has been suggested. In the vast majority of PEL cases Epstein-Barr virus (EBV) has been found in the tumour cells. We describe here an elderly human immune deficiency (HIV) seronegative man with intractable chest pain and pleural effusion. The diagnosis of malignant lymphoma was suggested cytologically and confirmed histologically following pleural biopsy. No lymphadenopathy or organ involvement with lymphoma was found. Systemic chemotherapy with a modified CHOP regimen with G-CSF support gradually led to the resolution of the chest pain and ultimately resulted in a complete clinical remission (CCR). The presence of HHV-8 was demonstrated by PCR using paraffin-embedded tissue samples from the involved pleura, whereas EBV-associated genetic material was absent. The patient remained in CCR for 18 months and died of an unrelated cause (cerebrovascular event). Only 11 other cases with clinical and virological features similar to those of our patient have been reported in the literature. Analysis of these rare cases suggests HIV-negative EBV-negative PEL to be a distinct clinical entity with epidemiological features resembling classical KS and supports an EBV-independent role for HHV-8 in the pathogenesis of PEL.     

T-cell/histiocyte-rich large B-cell lymphoma: a distinct clinicopathologic entity.

PURPOSE: Although it has proven difficult to delineate diagnostically reproducible and clinically relevant subgroups, the heterogeneity of diffuse large B-cell lymphomas (DLBCL) is widely acknowledged. In 1992, we reported on six cases that suggested that large B-cell lymphoma rich in stromal histiocytes and T cells may be identified as a distinct clinicopathologic entity within DLBCL. PATIENTS AND METHODS: An integrated clinicopathologic study of 40 cases of this DLBCL subtype is presented. RESULTS: Distinguishing a DLBCL rich in histiocytes and reactive T cells, designated T-cell/histiocyte--rich large B-cell lymphoma (THR-BCL), may be justified from a clinical point of view. The disease typically affects middle-aged male patients who usually present with advanced-stage disease that is not adequately managed with current therapeutic strategies. Whereas proliferation fraction and p53 overexpression, in addition to the clinical variables incorporated in the International Prognostic Index (IPI), significantly correlate with response to treatment and survival in a univariate analysis, only the IPI score identifies relevant prognostic THR-BCL subpopulations in a multivariate model. The morphologic and immunophenotypic profile of the neoplastic B cells in THR-BCL suggests that they may originate from a germinal center ancestor. CONCLUSION: THR-BCL constitutes a distinct clinicopathologic entity that is characterized by an aggressive behavior. Experimental therapeutic strategies may be indicated to obtain a more favorable response to treatment in this disease.     

Diffuse large B-cell lymphoma of the breast: a distinct entity?

The management of squamous cell carcinoma arising in the lungis markedly different than squamous cell carcinoma of the skin,cervix, or larynx. Likewise, the optimal management of diffuselarge B-cell lymphoma sometimes varies by the primary site ofinvolvement. Knowledge of the unique clinical behavior of lymphomaarising in certain extranodal sites is necessary. Examples ofthis include the requirement for specialized evaluation andtreatment of diffuse large B-cell lymphoma arising in the eye,brain, and testicle. It has also been questioned whether primarydiffuse large B-cell     

HTLV-I uveitis: a distinct clinical entity caused by HTLV-I.

Seroepidemiological, clinical and virological studies were carried out in an HTLV-I endemic area to find out if HTLV-I caused an intraocular inflammatory disorder, uveitis. The seroprevalence in patients with uveitis without defined etiologies (62/175, 35.4%) was significantly higher than that in patients with non-uveitic ocular diseases (42/261, 16.1%) or in patients with uveitis with defined etiologies (8/78, 10.3%). Moreover, the seroprevalence in young adults (20-49 years) with uveitis without defined etiologies was 30/67 (44.8%), whereas it was only 10/107 (9.3%) in the other two groups. The uveitis in HTLV-I carriers was characterized clinically by a moderate inflammation of the vitreous body accompanied by a mild iritis and retinal vasculitis. The proviral DNA of HTLV-I was detected by polymerase chain reaction from the inflammatory cells in the anterior chamber in 9 out of 9 seropositive patients with the uveitis, but not in any of the tested patients with other types of uveitis. These data, thus, indicate that HTLV-I causes a specific type of intraocular inflammation, uveitis.     

Primary mediastinal large B-cell lymphoma: clinical study of a distinct clinical entity and treatment outcome in 20 patients: review of the literature

Primary mediastinal B-cell lymphoma (PMBCL) is a discrete subset of large B-cell lymphoma with unique clinicopathologic features. The question of optimal treatment emerges because it is an uncommon but not rare occurrence. A retrospective study was therefore conducted in a group of patients in Greece to evaluate the clinical features and treatment outcome in this disease. Twenty patients with PMBCL, with a median age of 42 years, treated at centers participating in the Hellenic Cooperative Oncology Group over the last 20 years, were reviewed. Thirteen (65%) had bulky disease at the time of presentation, 7 (35%) had superior vena cavae obstruction, and 15 (75%) had extranodal involvement. All received doxorubicin-containing chemotherapy, followed in 11 cases by mediastinal radiotherapy. With a median follow-up of 91 months, the median survival is 67.7 months. These data are consistent with those reported from other centers concerning the patient's characteristics, natural history, response pattern to chemoradiation therapy, and prognosis. Response to therapy proved of prognostic significance. A key question that remains is the prompt identification of patients who would benefit from innovative or more intensive therapies.     

乳腺原发性淋巴瘤的临床病理及预后

目的 对乳腺原发性淋巴瘤的临床病理诊断、免疫表型进行分析.方法 对1998年1月至2007年5月诊治的乳腺原发性淋巴瘤8例,回顾性分析其临床表现、病理特征及免疫组织化学标记分型.结果 8例乳腺原发性淋巴瘤中,弥漫性大B细胞淋巴瘤5例,黏膜相关淋巴组织淋巴瘤2例,淋巴浆细胞性淋巴瘤1例.免疫组织化学标记,LCA、CD20、CD79a肿瘤细胞膜阳性;CD45RO、CD3、CD23、CD10、CD5肿瘤细胞阴性.临床分期,5例为ⅠE期,3例为ⅡE期.采用CHOP方案化疗,随访2～110个月,其中1例随访108个月后,另一侧乳腺肿瘤复发.结论乳腺原发性淋巴瘤主要为B细胞淋巴瘤,以弥漫性大B细胞淋巴瘤和黏膜相关淋巴组织淋巴瘤较多见,而淋巴浆细胞性淋巴瘤少见.对于临床ⅠE期和ⅡE期的早期患者,采用CHOP方案化疗有较好的治疗效果.     

Cutaneous malignant lymphoma: a clinical and pathological study of 13 cases

Thirteen cases of malignant lymphoma, exclusive of mycosis fungoides, with initial involvement of the skin, were selected from 391 consecutive patients with non-Hodgkin's lymphoma. Their clinical course was correlated to histological subtype. All patients (5/5) with 'favourable' histology had single indurated plaques without extracutaneous involvement, and remained in complete remission for at least 5 years after local radiation therapy. In contrast, all those with 'unfavourable' histology not lost to follow-up (7/7) suffered relapse or died within a 2-year period. They generally had multiple skin lesions and extracutaneous involvement at diagnosis or shortly afterwards. We conclude that histological subtype is an important variable in predicting clinical course in those with cutaneous malignant lymphoma.     

Intradural clival chordoma: a rare pathological entity

Chordomas constitute about 1% of intracranial tumors. They are generally extradural destroying the bone. Intradural chordomas are very rare. We present one such case of a clival intradural chordoma who presented with a left trigeminal nerve sensory neuropathy. The lesion was totally excised uneventfully via a retromastoid suboccipital approach. There was no recurrence of the lesion at 1-year follow-up. Characteristics of intradural chordoma and its close differential ecchordosis physaliphora are reviewed in this article.     

Follicular lymphoma without t(14;18) and with BCL-6 rearrangement: a lymphoma subtype with distinct pathological, molecular and clinical characteristics.

Translocations involving the BCL-6 gene are frequently observed in diffuse large B cell lymphoma, but have rarely been reported in follicular lymphoma (FL). We studied a distinct cohort of FLs with a 3q27/BCL-6 gene rearrangement, but lacking the t(14;18) translocation. In 13/15 cases, translocations involved the 3q27 and the 14q32 regions. All cases displayed a marked follicular growth pattern and, in some instances, a monocytoid component. Tumor cells were CD5(-) CD20(+) CD23(-) CD43(-) BCL-6(+), and in the main CD10 negative (n = 10, 71%) and BCL-2 negative (n = 11, 78%). When compared to 20 typical t(14;18)(+) FLs, the presence of large follicles (P = 0.01) and a CD10(-)/BCL-2(-) phenotype were more frequently observed (P = 0.001) in our cohort. Clonal mutations arising in the BCL-6 first intron were observed in 5/7 cases with evidence of intraclonal heterogeneity, consistent with a germinal center origin. No significant difference was found in comparison to t(14;18)(+) FL regarding age, sex, performance status, bone marrow involvement or overall survival. However, in the 3q27(+) FL group, a stage III/IV disease and a bulky mass were less frequently observed. This study indicates that 3q27(+) FL without t(14;18) translocation have peculiar clinico-pathologic features and may correspond to a rare and distinct subtype of lymphoma originating from the germinal center.     

Primary cutaneous large B-cell lymphoma of the legs: a distinct clinical pathologic entity treated with CD20 monoclonal antibody (rituximab)

Primary cutaneous large B-cell lymphoma of the legs (PCLBLL) is most commonly diagnosed in the elderly, and is generally confined to the lower parts of one or sometimes both legs. Despite treatment with radiotherapy, relapses and extracutaneous involvement can occur, and unlike other low-grade cutaneous-B-cell non-Hodgkin's lymphomas (NHLs), the prognosis is variable, with an estimated 5-year survival rate of 58%. This report describes the case of an 81-year-old man who was diagnosed with PCLBLL. Staging evaluation did not reveal NHL elsewhere. The patient declined recommendations to receive cytotoxic chemotherapy. Instead, he was treated with anti-CD20 monoclonal therapy (rituximab) and his cutaneous lesions completely regressed during a 16-week period. This report suggests that rituximab is a therapeutic option for those patients with PCLBLL who may not be good candidates to receive radiation therapy or chemotherapy. Long-term follow-up and greater experience with rituximab in a variety of clinical settings will ultimately determine the appropriate role of this costly, but relatively safe, antibody-based therapy for CD20+ expressing NHLs.     

Oligometastatic gastric cancer: An emerging clinical entity with distinct therapeutic implications

Gastric cancer (GC) remains responsible for a high burden worldwide being the third leading cause of cancer-related mortality. Most of patients present at an advanced stage at diagnosis and are thus candidates to standard chemotherapy resulting in median survival of less than 1 year. Oligometastatic gastric cancer is an increasingly recognized clinical entity characterized by limited metastatic spread that has been showing to benefit from aggressive multimodality strategies encompassing chemotherapy and surgery. The ongoing RENAISSANCE/AIO-FLOT5 (NCT02578368) phase III trial is aimed at evaluating if perioperative chemotherapy with FLOT in combination with surgical resection of the primary tumour and metastases could become the new standard of care for oligometastatic GC. In the meantime, in addition to currently available clinical parameters, the emerging predictive/prognostic role of biomarkers such mismatch repair deficiency/microsatellite instability high status needs to be specifically addressed also in this subgroup of GC to assist in patient selection.     

Helicobacter pylori-related diffuse large B-cell lymphoma of the stomach: a distinct entity with lower aggressiveness and higher chemosensitivity

We recently showed that Helicobacter pylori (HP)-positive gastric ‘pure'' diffuse large B-cell lymphoma (DLBCL) may respond to HP eradication therapy. However, whether these HP-related ‘pure'' DLBCL of the stomach may differ fundamentally from those unrelated to HP remains unclear. In this study, we compared the clinicopathologic features of these two groups of patients who had been uniformly treated by conventional chemotherapy. Forty-six patients were designated HP-positive and 49 were HP-negative by conventional criteria. HP-positive patients had a lower International Prognostic Index score (0–1, 65% vs 43%, P=0.029), a lower clinical stage (I-IIE1, 70% vs 39%, P=0.003), a better tumor response to chemotherapy (complete pathologic response, 76% vs 47%, P=0.004) and significantly superior 5-year event-free survival (EFS) (71.7% vs 31.8%, P<0.001) and overall survival (OS) (76.1% vs 39.8%, P<0.001). To draw a closer biologic link with HP, HP-positive tumors were further examined for CagA expression in lymphoma cells. Compared with CagA-negative cases (n=16), CagA-positive cases (n=27) were associated with high phosphorylated SHP-2 expression (P=0.016), and even better 5-year EFS (85.2% vs 46.3%, P=0.002) and OS (88.9% vs 52.9%, P=0.003). HP-related gastric ‘pure'' DLBCL may be a distinct tumor entity, which is less aggressive, and responds better to conventional chemotherapy.