An association between cutaneous melanoma and non-Hodgkin's lymphoma: pooled analysis of published data with a review.

BACKGROUND: Several epidemiological studies have suggested an association between cutaneous melanoma and non-Hodgkin's lymphoma. METHODS: We pooled the data from seven cohort studies and calculated the risk of secondary occurrence of cutaneous melanoma after non-Hodgkin's lymphoma, and of non-Hodgkin's lymphoma subsequent to the occurrence of cutaneous melanoma. RESULTS: There were 137 612 patients with primary non-Hodgkin's lymphoma and 109 532 patients with primary cutaneous melanoma. We found a statistically significant increased risk of non-Hodgkin's lymphoma among cutaneous melanoma survivors [standardised incidence ratio (SIR) 2.01, 95% confidence interval (CI) 1.79-2.24] and cutaneous melanoma among non-Hodgkin's lymphoma survivors (SIR 1.41, 95% CI 1.26-1.58). CONCLUSION: Our study confirmed an association between cutaneous melanoma and non-Hodgkin's lymphoma occurring in the same patient indicative of a need to examine further the role of the common risk factors.     

Cutaneous malignant melanoma and neurofibromatosis type 1

Neurofibromatosis 1 (NF1) is a genetically transmitted disease occurring approximately once in 3000 live births and resulting from mutations of the NF1 gene that encodes a protein named neurofibromin, a negative regulator of the ras-dependent pathway. An excess of neoplasia especially tumours of neuroectodermal origin is classically observed. The occurrence of malignant melanoma in patients with NF1 has already been described in scattered clinical reports but little is known as to the characteristics of melanoma arising in NF1 patients. A multicentric retrospective study was conducted on a panel of French referring centres for a period of 13 years to identify patients with both melanoma and NF1. Patients with mucosal or ocular melanoma were excluded. The diagnosis of malignant melanoma was based on specific histology whereas NF1 was identified according to the criteria proposed by the NIH Consensus Conference. All patient fulfilling criteria for both melanoma and NF1 were investigated using a common procedure recording clinical and histological data along with prognostic factors for the two diseases. Eleven patients were identified with both diseases. The clinical pattern of NF1 was quite similar to the classical form of the disease, but some unusual features were present as regards to the melanoma: a sex-ratio of 10 women for one man and an average age lower than expected (median age=33 years) for melanoma occurrence. Among prognostic factors, median thickness was high compared to large series of melanoma in the literature (3.20 versus 1.5 mm). Another neoplasia occurred in three patients. An increase in melanoma incidence in patients with NF1 remains hypothetical but our small series of malignant melanoma arising in NF1 patients displays a large female preponderance, a higher thickness than expected and a frequent association with a second neoplasia. The peculiar female proneness for cancer whatever its localization and the risk of multiple neoplasias have already been reported in NF1 patients and could be true for malignant melanoma as well.     

Observations of second primary malignancy in patients with multiple myeloma

BackgroundAdvances in the treatment of multiple myeloma have resulted in immunomodulatory (IMiD) agents becoming integral to the standard treatment armamentarium. IMiD agents are effective in the initial and relapsed settings of multiple myeloma. Three studies evaluating the duration of remission in maintenance lenalidomide vs. placebo reported an increased incidence of second primary malignancies in patients receiving maintenance therapy. The purpose of this study was to evaluate the incidence of second primary malignancies after IMiD exposure for standard induction and relapsed therapy in myeloma.Patients and MethodsA retrospective chart review was conducted at the Indiana University Simon Cancer Center in Indianapolis, Indiana. Patients were older than 18 years and had been diagnosed with multiple myeloma. Patients with a previous diagnosis of cancer were excluded. The primary objective was to assess the incidence of second primary malignancies in all patients. Secondary objectives included the type of malignancy, whether patients had been previously treated with IMiD therapy and the time from treatment initiation to diagnosis of a second malignancy.ResultsThree hundred twenty-five patients were reviewed and 279 were included in the study. Ten patients were diagnosed with a second primary malignancy (3.5%). Nine of the 10 patients were treated with IMiD therapy before diagnosis (P = .169). The mean time to diagnosis was 360 days for all patients.ConclusionThe incidence of second primary malignancy was not statistically significant in the IMiD-treated patients. Further long-term follow-up is needed to better assess the potential adverse events of these novel agents.     

Lung cancer as a second primary.

An unusually high association of other primary cancers (9.7%) was found during the analysis of 403 consecutive cases of carcinoma of the lung diagnosed at DGMC between 1960 and 1975. Incidence by stage included 17.3% for Stage I (75 cases) and 16.9% for Stage II (59 cases). Median survival by stage was not adversely affected by the associated malignancy. Incidence by histologic type was 15.6% for adenocarcinoma (132 cases), 7.7% for epidermoid (130 cases), 1.5% for oat (small cell) (67 cases), 12.5% for large cell (40 cases) and 11.8% for undifferentiated anaplastic type (34 cases). Of 31 cases of Stage I adenocarcinoma, 9 (29%) had second malignancies. Both adenocarcinoma and epidermoid carcinoma exhibited decreasing association of second malignances with increasing stage of lung cancer. The head and neck region was the location of the nonlung malignancy in 22 cases and the GU system in 11 cases. Two cases each of colon carcinoma and basal cell skin carcinoma were found and there was one case each of carcinoma of the pancreas, lymphoma and melanoma. The diagnosis of lung cancer was made first in only 3 instances. The appearance of solitary nodules in patients with known malignancy should receive strong consideration for vigorous diagnostic and therapeutic procedures. Future studies should consider carcinogenic stimuli that may be common etiologic factors in both malignancies.     

Malignant melanoma and carcinoma of the breast.

Five patients with breast cancer and malignant melanoma are reported. Two patients had a third primary malignancy. In 4 out of 5 patients the breast tumor was the initial tumor discovered, and in 4 out of 5 the second tumor evolved metachronously. No specific carcinogenic factor could be established. The low malignancy potential of the melanoma by pathologic criteria may explain the lack of previous reports of this association.     

7 例鼻中隔恶性肿瘤的临床诊治分析*

目的:探讨鼻中隔恶性肿瘤的临床诊断与治疗方法。方法:收集1993年2 月至2009年10月天津市第一中心医院收治7 例原发于鼻中隔的恶性肿瘤患者的临床资料,分别采用鼻内镜或鼻外径路或唇正中切口面部翻揭手术加放疗或化疗,并对生存状况进行回顾性分析。结果:恶性淋巴瘤1 例经病理证实术后予化疗和放疗,其余6 例包括腺样囊性癌3 例、恶性黑色素瘤1例、软骨肉瘤1 例、乳头状瘤恶变1 例。随访2～16年,2 例分别于术后2 年及3 年4 个月因复发或转移而死亡,其余5 例生存、未见肿瘤复发。结论:对于原发于鼻中隔的恶性肿瘤以手术切除为主（恶性淋巴瘤除外）,关键是一次性彻底切除,术后应采取放化疗等综合治疗,并予严密随访。      

Sub-clinical dissemination of follicular lymphoma in normal sized lymph nodes may not be detected by radiologic staging: a case of disseminated follicular lymphoma detected in nodal clearance as part of therapy for cutaneous melanoma

Patients with localized follicular lymphoma are potentially curable; however, the failure rate for local treatment suggests that a proportion of apparently localized disease is being under-staged. We report a case of incidentally diagnosed follicular lymphoma found in association with a stage II malignant melanoma, with immunohistochemical evidence of disseminated lymphoma in radiologically and clinically benign regional lymph nodes. This case provides some evidence to the cause of treatment failure in patients with clinically localized follicular lymphoma, and is a histologically proven example of the association between melanoma and lymphoma.     

β-adrenergic-blocking drugs and melanoma: current state of the art

The purpose of this review is to present the preclinical, epidemiological and clinical data relevant to the association between β-blockers and melanoma progression. Preclinical studies have shown that β-adrenergic receptor (β-AR) signaling can inhibit multiple cellular processes involved in melanoma progression and metastasis. These observations have suggested the possibility that drugs originally intended for the treatment of cardiovascular disease, the β-AR blockers, may provide new therapeutic opportunities for the control of tumor progression. A large number of observational studies demonstrated the protective effect of β-blockers in breast cancer but, more recently, similar findings were also reported in other cancers such as prostate cancer and melanoma. With regard to melanoma, two recently published studies demonstrated a great reduction in the risk of disease progression for each year of treatment with β-blockers. The results from these studies have suggested a potential role for targeting the β-AR pathway in melanoma patients. Questions regarding the type of β-blocker or tumor characteristics, appropriate treatment paradigms and, most importantly, efficacy must be answered in randomized clinical studies before β-blockers can be considered a therapeutic option for patients with melanoma.     

Malignant melanoma appearing in a post-mastectomy lymphedematous arm: a novel association of double primary tumors

The association of a malignant melanoma appearing as an additional primary tumor in the swollen arm adjacent to a mastectomy for breast cancer is reported. A review of the literature revealed only one similar patient previously reported. In both patients, the melanoma and its metastasis were restricted to the lymphedematous arm, appeared 10 years post-mastectomy, and responded to therapy. The similarity to Stewart-Treves syndrome is emphasized. It is suggested that nevi developing in the lymphedematous arm post-mastectomy should be carefully monitored and excised early whenever indicated.     

Second malignancy after treatment of childhood non-Hodgkin lymphoma.

BACKGROUND: The objective of this report was to determine the cumulative incidence of and risk factors for second malignancy and the competing risk of death due to any other cause among patients who were treated for childhood non-Hodgkin lymphoma (NHL). METHODS: The authors retrospectively reviewed a cohort of 497 patients with NHL who were treated at St. Jude Children's Research Hospital between 1970 and 1997. RESULTS: A second malignancy developed in 16 patients (9 patients with solid tumors and 7 patients with secondary acute myeloid leukemia [AML]). This number was 10.8-fold (95% confidence interval, 6.1-16.9) higher than the 1.48 patients projected for the general population by SEER Cancer Statistics. The estimated cumulative incidence rate of second malignancy was 2.1% +/- 0.7% at 10 years after diagnosis of NHL and increased to 4.8% +/- 1.3% at 20 years after diagnosis. The cumulative incidence rate of second malignancy was least among patients with small noncleaved cell lymphoma (0.5% +/- 0.5% at 20 years), higher among patients with large cell lymphoma (5.8% +/- 3.3% at 20 years), and highest among patients with lymphoblastic lymphoma (10.9% +/- 3.6% at 20 years; P = 0.002 for overall comparison). Exposure to epipodophyllotoxins was a risk factor for the development of secondary AML (P < 0.001). The cumulative incidence rate of death due to other causes was significantly less for patients who were treated after June 1978 (19.9% +/- 2.2% at 10 years) compared with patients who were treated earlier (55.6% +/- 4.2% at 10 years; P < 0.001), whereas the risk of second malignancy was similar for these two eras. CONCLUSIONS: Survivors of childhood NHL, especially those with lymphoblastic histology, are at a greater risk of developing a second malignancy compared with the general population. The incidence rate of second malignancy has remained unchanged despite a recent decline in the risk of death related to primary NHL or earlier treatment complications.     

Primary central nervous system lymphoma as a secondary malignancy

Primary central nervous system lymphoma (PCNSL) is a rare neoplasm, but it is occurring with increased frequency even among apparently immunocompetent patients. Although secondary malignancies frequently involve the lymphoreticular system, PCNSL has been reported as a second neoplasm only once previously. Seven patients are discussed who developed PCNSL after successful treatment for a prior neoplasm. The original cancer was colon (one), breast (one), thyroid (one), Hodgkin's disease (two), and non-Hodgkin's lymphoma (two). Patients with systemic non-Hodgkin's lymphoma were thought to have a separate cerebral lymphoma on the basis of a prolonged disease-free interval from their systemic lymphoma, and the absence of systemic disease, when PCNSL was diagnosed and through subsequent follow-up. The PCNSL developed a median of 10 years after the diagnosis of the first tumor and 6 years after the last evidence of systemic disease. The diagnosis of PCNSL was often delayed because of confusion with brain metastases, and initial shrinkage or disappearance of the lesion after corticosteroids. Formation of PCNSL may be a consequence of treatment for the first malignancy, reflect an unidentified inherent predisposition to neoplastic transformation, or result from the changing epidemiology of PCNSL in the general population. These mechanisms are not mutually exclusive, and a single hypothesis cannot account for all these cases.     

Veterans with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have a markedly increased rate of second malignancy, which is the most common cause of death

Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have an increased incidence of high-grade lymphoid malignancy. The risk of non-lymphoid second malignancy in this population is not well-defined to date. To test the hypothesis that patients with CLL/SLL have an increased risk of second malignancy, we studied the rate of second malignancy in 132 CLL/SLL patients and compared it to the rate of malignancy (excluding non-melanomatous skin cancer) in the Central Arkansas Veterans Healthcare System population of approximately 38,000 veterans over a period of 11.5 years. The rate of second malignancy, diagnosed concomitantly or after CLL/SLL, and the age-adjusted rate of malignancy calculated from tumor registry reports and demographic data, were used to calculate a Standardized Morbidity Ratio (SMR) with 95% confidence interval (CI). Twenty-one (16%) of the CLL/SLL patients had second malignancies (19 non-lymphoid, 1 Richter's transformation and 1 Hodgkin's disease), which were fatal in 15 (71%) patients. The SMR for the CLL/SLL population was 2.97 (95% CI 1.84 - 4.55) for second malignancy and 2.69 (95% CI 1.62 - 4.21) for non-lymphoid second malignancy. This study of a well-defined CLL/SLL population shows a significantly increased risk of second malignancy, which was the primary cause of death for 9% of all CLL/SLL patients (34% of all patient deaths).     

Double primary cancers of the prostate and bladder: a literature review

A number of studies report a high frequency of double primary cancers of the bladder and prostate. The coincidence was as high as 70% for prostate cancers in patients with bladder cancer, and 3.4% for bladder cancers in patients with prostate cancer. Two studies reviewing medical records reported a significant risk of bladder cancer after prostate cancer and of prostate cancer after bladder cancer. Only 1 of 3 cancer registry studies reported a significantly increased risk of prostate cancer after bladder cancer, and 3 of 11 studies reported a significantly increased risk in bladder cancer after prostate cancer. There was an association between DNA repair and N-acetyltransferase polymorphisms and risk of prostate and bladder cancer. These data suggest that these cancers may share a common carcinogenic process or that these patients are particularly susceptible to both cancers. Because of the association between these cancers, patients who are diagnosed with prostate or bladder cancer should be followed closely for the detection of the second urologic malignancy.     

Prevalence of hepatitis C infection in patients with non-Hodgkin's lymphomas

Several studies have suggested an association between hepatitis C virus (HCV) and low-grade B-cell non-Hodgkin's lymphomas. The results, however, have been controversial. Italian and Japanese studies have reported a 40% prevalence rate, but the data were not confirmed by English and Canadian studies. We evaluated the prevalence of HCV infection in 109 patients with non-Hodgkin's lymphomas, and compared it with a control group composed of 67 patients with Hodgkin's disease and 31 patients with chronic lymphocytic leukemia. The prevalence of HCV infection was also determined in blood donors. HCV infection was detected using second and third generation anti-HCV ELISA. Positive results were additionally confirmed using Inno-LIA AbIII and/or RNA-HCV by PCR. Immunohistochemical stains were used to determine B or T cell lineage when the morphological analysis was not sufficient for lymphoma classification. HCV infection was detected in 9% of patients with non-Hodgkin's lymphomas, in 2% of patients in the control group (p=0.036), and in 1.2% of blood donors. There was no difference in the prevalence of HCV infection between patients with B or T cell lymphomas. Blood transfusions or previous surgeries, both risk factors for HCV infection, were detected in 90% of the patients with a positive anti-HCV test, in average 17 and 36 years before the diagnosis of lymphoma, respectively. Seventy percent of the patients with non-Hodgkin's lymphomas and a positive anti-HCV test presented evidence of chronic liver disease when the lymphoma was diagnosed. This study suggests the presence of an association between HCV infection and non-Hodgkin's lymphomas in Brazil.     

Malignant Melanoma in an HIV-Infected Man: A Case Report and Literature Review

Malignant Melanoma in an HIV-infected Man: A Case Report and Literature Review

Although it is not proven by causative association, several studies indicate that patients with acquired immune deficiency syndrome (AIDS) have a high risk for developing cutaneous malignancies, especially lymphoma and Kaposi's sarcoma. Other malignant cutaneous lesions seen in this patient population include basal-cell carcinoma, squamous-cell cancer, Bowen's disease, and rarely, maligtiant melanoma. We review the clinical course of a human immunodeficiency virus (HTV)-infected man with a superficial spreading melanoma of the scapula treated with wide local excision. Ten years later, he was diagnosed as having metastatic and widespread disease. By placing our patient's experience in context with other case reports, we sought to determine whether malignant melanoma in the HIV-infected population presents atypically or has a more aggressive natural history. The appearance of malignant melanoma in homosexual men may be coincidental or reflective of the expanding spectrum of HTV-associated diseases. Of the 22 patients reported to have malignant melanoma and HIV, approximately one-third had metastatic disease at the time of initial examination, and those with a decreased CD4⁺ cell count were most likely to have systemic symptoms. Melanomas among patients with HIV infection were often atypical in appearance, being multiple or metastatic, as is the case in other well-defined immunosuppressed groups. Further epidemiological and clinical studies are required to determine whether melanoma occurs more frequently or is more likely to metastasize in persons with HTV disease. Laboratory investigators must also concentrate on those factors in the setting of HIV disease that may contribute to melanocyte activation. Our patient's fulminant clinical course should alert clinicians to carefully evaluate patients with HIV infection and unusual pigmented cutaneous lesions, or who have a prior history of malignant melanoma.     

Second non-germ cell malignancies after radiotherapy of testicular cancer with or without chemotherapy

The incidence of a new primary non-germ cell malignancy was determined in 876 patients with testicular cancer treated at the Norwegian Radium Hospital from 1956 to 1977. Sixty-five patients developed a second cancer leading to a statistically significant increased relative risk (RR = 1.58), especially if extended radiotherapy had been given (RR = 4.13). The excess risks of developing lung cancer and malignant melanoma were 2.03 and 3.89, respectively. Increased RR for these two cancer types were seen both after extended radiotherapy and after radiotherapy combined with chemotherapy. Studies of the time between treatment and secondary lung cancer indicated that the development of the new lung cancer could be partly treatment related, whereas the raised incidence of malignant melanoma may be related to the frequent health checks performed in patients with testicular cancer. Patients who had received extended radiotherapy were also at an increased risk of developing cancer of the stomach and of the colon. Three cases of acute leukaemia were observed more than 5 years after treatment, all of them in patients who had received abdominal radiotherapy only. It is concluded that patients apparently cured of a testicular cancer have an increased risk of developing a new treatment related non-germ cell malignancy, in particular lung cancer. The application of the extended radiotherapy or the combination of radiotherapy and chemotherapy containing alkylating drugs should be avoided in order to reduce this excess risk.     

自身免疫与淋巴瘤

 自身免疫和淋巴瘤之间有双重相关性,即自身免疫性疾病患者淋巴瘤发生率增高,同时淋巴瘤患者易合并自身免疫现象。现对自身免疫性疾病患者发生淋巴瘤和淋巴瘤患者合并自身免疫现象的流行病学情况、临床特点以及内在机制等方面的新进展进行综述。     

Phase III Trial of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (Chop) Versus Cisplatin, Etoposide, Bleomycin and Prednisone (CisEBP) for the Treatment of Advanced Non-Hodgkin's Lymphoma of High Grade Malignancy

The trial included 85 previously untreated patients (median age 61 years) with stage III or IV non-Hodgkin's lymphoma (NHL) of the subtypes centrocytic lymphoma, diffuse centroblastic lymphoma, immunocytoma, immunoblastic lymphoma, or unclassified lymphoma of high grade malignancy. The patients were randomized to 9 monthly treatment cycles of CHOP (cyclophos-phamide, doxorubicin, vincristine, prednisone) or CisEBP (cis-platin, bleomycin, etoposide, prednisone). Patients who had failed to achieve even a partial response (PR) after the completion of 2 cycles were switched to the alternative regimen. Complete response (CR) on primary treatment was obtained in 70% (55-83%) of CHOP-treated patients and in 25% (13-41%) of CisEBP-treated patients (p = 0.0004). Secondary CHOP treatment produced CR in 7 (30%) of 24 patients and secondary CisEBP treatment led to CR in 2 (15%) of 14 patients. The median survival was 3.4 years in the CHOP arm and 2.6 years in the CisEBP arm (p = 0.78). Hematologic toxicity was mainly leukocy-topenia and anemia in both treatment arms. Non-hematological toxicity was slight, and late toxicity was insignificant. Three treatment-related deaths were noted. We conclude that CHOP induces more remissions than CisEBP in advanced lymphomas of high grade malignancy.     

Hepatitis B virus infection and B-cell non-Hodgkin's lymphoma in a hepatitis B endemic area: a case-control study.

Several studies have reported a higher prevalence of chronic hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma and suggested a pathogenic role for HCV, but studies on hepatitis B virus (HBV) infection and non-Hodgkin's lymphoma are limited. To determine the association between HBV infection and non-Hodgkin's lymphoma, we performed a case-control study in Korea, a hepatitis B endemic area. We recruited 222 patients newly diagnosed with non-Hodgkin's lymphoma at Seoul National University Hospital between January 1997 and December 1998 as cases. Four age- and sex-matched controls were selected for each case, and the control groups comprised of 439 patients with non-hematological malignancy (control group 1) and 444 subjects with non-malignant conditions (control group 2). Relative risk of developing non-Hodgkin's lymphoma among individuals tested positive for hepatitis B surface antigen was calculated after controlling for other potential risk factors of lymphoma, such as smoking, alcohol drinking, transfusion history and HCV infection. Hepatitis B surface antigen was positive in 28 of 222 patients (12.6%) with non-Hodgkin's lymphoma compared with 32 of 439 (7.3%) in control group 1, and 21 of 444 (4.7%) in control group 2 (P = 0.001). The crude odds ratio for B-cell non-Hodgkin's lymphoma among the HBV carriers was 2.54 (1.46 - 4.45) and the adjusted odds ratio was 3.30 (1.69 - 6.45) by multivariate analysis. The present study suggests that the risk of B-cell non-Hodgkin's lymphoma is increased in HBV carriers and warrants further investigation of the possible role of hepatitis B virus in the pathogenesis of B-cell non-Hodgkin's lymphoma.