Primary malignant lymphoma of the breast: Mammographic and ultrasonographic findings

Malignant lymphoma rarely involves the breast. We describe four cases of primary breast lymphoma encountered in our institution from 1979 through 1996, focusing on mammographic and ultrasonographic findings. The lymphomas were demonstrated by mammography as a well-defined mass in one case, an ill-defined mass in two cases and as diffuse increased opacity in one case. No desmoplastic change or calcification was noted. In 3 cases ultrasonography was used, revealing hypoechoic masses with (1 case) or without (2 case) posterior enhancement. During the past two years, 45 of 197 cancers (23%) were demonstrated as a mass without desmoplastic change or calcification by mammography and ultrasonography at our institution. It can be difficult to distinguish malignant lymphoma from more common diseases of the breast, such as carcinoma, by mammography and ultrasonography.     

恶性肉芽肿与中线淋巴瘤的临床观察

目的探讨恶性肉芽肿与中线淋巴瘤两种疾病的关系。方法自１９８９年１２月至１９９５年３月共收治恶性肉芽肿及中线淋巴瘤各２３例。两者在发病年龄、部位及首发症状相似。前者有７３．９％单用放射治疗,后者有６９．５％用放射治疗和化疗联合。病理类型前者为炎性坏死性肉芽组织,后者均为非霍奇金淋巴瘤（Ｔ细胞性１３例,Ｂ细胞性１例,未分型９例）。结果完全缓解率分别为８２．６％和６５．２％,２年生存率分别为８２．６％和７３．９％。结论两者不应视为同一疾病。     

An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma

An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.     

Case of early malignant lymphoma scattered over the whole stomach

Early malignant lymphoma is rare and cases with scattering over the whole stomach are extremely rare. Malignant lymphoma is frequently accompanied by R.L.H. or multiple malignant lymphoma. In our case, some lesions were difficult to distinguish from reactive lesions because cellular atypia was of a low grade. As preoperative radiograpic and endoscopic examination had suggested the lesions to be widespread, the surgical stump was carefully inspected to avoid leaving malignant cells. We discuss the surgical treatment of malignant lymphoma of the stomach.     

Primary gastrointestinal lymphomas: a classification of 66 cases.

Using routine histology, resin embedded sections and immunohistochemical techniques on formalin-fixed, paraffin processed tissue, 66 cases of primary gastrointestinal lymphoma have been classified. This study necessitated the development of reliable criteria to separate lymphomas of true histiocytic origin from those of lymphocytic origin. Among the morphologic properties of malignant histiocytes were complex pleomorphic nuclei, abundant well delineated cytoplasm and phagocytosis. These cells were shown to contain all major immunoglobulin chains, C3, lysozyme and in some cases alpha 1 antitrypsin. Malignant lymphomas derived from histiocytes could be divided into two groups: malignant histiocytosis of the intestine (MHI), a recently described diffuse pleomorphic lymphoma associated with villous atrophy of the small intestine, and histiocytic lymphoma (HL) which forms solid tumor masses in a similar manner to lymphocyte derived tumors. Immunohistochemical studies of lymphocyte derived tumors were negative apart from one case with plasmacytoid differentiation. Of the 66 cases, 50% were of histiocytic origin (33% MHI, 17% HL) and 41% of lymphocyte origin, there was one case of Hodgkin's disease and five cases were unclassified. The role of the histiocyte in gastrointestinal mucosa deserves further study.     

Malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms

BACKGROUND: The purpose of the current study was to determine the distribution and relative frequency of each subtype of malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms (REAL). METHODS: The pathology files of a regional hospital in southern Taiwan for 1989-1998 were searched for malignant lymphoma, lymphoproliferative disorder, and Hodgkin disease (HD). The results of light microscopy, immunohistochemistry, and in situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were correlated with clinical findings, and all cases were classified according to REAL. RESULTS: A total of 205 cases were analyzed retrospectively. There were 197 cases (96.1%) of non-Hodgkin lymphoma (NHL) and 8 cases (3. 9%) of HD. Among the 197 NHL cases, 161 (81.7%) were of B-cell lineage and 36 (18.3%) were of T-/natural killer cell lineage. Diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, and follicular lymphoma were the most common B-cell subtypes and represented 47.2%, 19.3%, and 6.1%, respectively, of all NHL cases. Among the 36 cases of T-/natural killer cell lineage, unspecified peripheral T-cell lymphoma (8.6%), T-/natural killer cell lymphoma (angiocentric lymphoma) (4.1%), and anaplastic large cell lymphoma (3.6%) were the most common subtypes. Seven of eight T-/natural killer cell lymphoma cases were positive for EBER. The eight cases of HD were classified as lymphocyte-rich classic (two cases), nodular sclerosis (two cases), and mixed cellularity (four cases) subtypes. Three of these eight cases were positive for EBER. CONCLUSIONS: To the authors' knowledge this study is the first in Taiwan using the REAL classification and it again confirms the different geographic distribution of the various subtypes of malignant lymphoma. The frequency of T-/natural killer cell lineage NHL in Taiwan is higher than that in Western countries but not as high as reported previously.     

Malignant lymphoma in four of five siblings.

In one family four out of five siblings were affected with malignant lymphoma and HD has been diagnosed in two other relatives. HLA-haplotypes were identical for the three diseased siblings who were so studied, whereas for the unaffected one they were different.     

脊椎恶性淋巴瘤(18例报告)

目的 提高脊椎恶性淋巴瘤诊断与治疗的水平。方法 1974—2000年回顾性分析脊椎恶性淋巴瘤18例，男12例，女6例，平均年龄31．3岁。颈胸椎1例，胸椎10例，胸腰椎1例，腰椎6例，分析临床资料，x摄线片，CT和MRI的特点。结果 13例(72．2％)腰背部持续性疼痛、消瘦、盗汗、380C～39℃不规则发热，不同程度脊髓或马尾损害13例，8例(44．4％)酷似脊椎结核。脊椎x线摄片无特异性改变，难与脊椎结核鉴别；4例胸部摄片纵隔阴影扩大。MRI矢面T1W增强后，将脊椎淋巴瘤分为三型：硬膜外型，椎旁和椎体型。合并截瘫或马尾受累外科手术切除，随后放疗或／和化疗，可获得较好疗效。结论 对诊断不明确，特别并脊髓或马尾损害应行活检或手术探查，早期诊断，早期治疗。     

True histiocytic lymphoma. A report of four cases

Clinical, morphologic, cytochemical, immunologic, and ultrastructural features of four cases of true histiocytic lymphoma are described. The neoplastic cells were large, ranging from 20 to 45 mu in diameter with round, folded, or convoluted nuclei, and abundant eosinophilic cytoplasm. They exhibited diffuse nonspecific esterase activity. Diffuse acid phosphatase activity was present in two cases so tested. Muramidase activity was present in half of the cases. Finely granular PAS-positive material was seen in the cytoplasm. Methyl green-pyronin positivity was variable. An occasional neoplastic cell showed erythropagocytosis in one case. Malignant cells either contained no cytoplasmic immunoglobulins (three cases) or had immunoglobulins of multiple classes (one case). Surface markers were studied in two cases; they were absent in one case, and were of multiple classes in another case. Ultrastructurally the neoplastic cells had lysosomal granules in three cases so examined, and phagolysosomes, phagocytized material and residual bodies in one of three cases so studied. Patients ranged in age from 28 to 60 years. Two patients had extralymphatic tumors. Survival of more than 5 years was seen in one patient.     

Evaluation of rIFN-gamma in the treatment of lymphoma and melanoma of the skin by systemic and intralesional administration

This study evaluated the clinical effect of rIFN-gamma for the treatment of lymphoma and melanoma of the skin by systemic intravenous and intralesional administration. By intravenous drip infusion, one of two cases of mycosis fungoides (stage IV) showed CR of skin lesions by administration of a total of 160 X 10(6) units, 4 or 8 X 10(6) units, every other day for 3 months. The remaining case was, however, in a state of PD. Intralesional administration of rIFN-gamma to six cases of cutaneous lymphoma, including three cases of mycosis fungoides, two cases of cutaneous T cell lymphoma, and one case of adult T cell lymphoma, resulted in three cases of CR, two cases of MR and one case of PD. In contrast, four cases of malignant melanoma, two of which received systemic administration and two intralesional administration, did not show any obvious clinical response, one showing PR and the other three PD. Histopathological examination of skin lesions before and after administration of rIFN-gamma indicated that the cutaneous lymphoma lesions were initially infiltrated by lymphocytes and macrophages, and that later on, they were free from tumor cells. Our study indicates that rIFN-gamma appears to provide a new modality for the treatment of cutaneous lymphoma by systemic and intralesional administration.     

Epidemiological study of socioeconomic factors and clinical findings in Hodgkin's disease, and reanalysis of previous data regarding chemical exposure

An association between malignant lymphoma (both Hodgkin's disease (HD) and non-Hodgkin lymphoma) and exposure to organic solvents, phenoxy acids, or chlorophenols was previously reported. A reanalysis of this investigation regarding the cases with HD and exposure to various chemicals was performed and resulted in comparable findings to the whole group of malignant lymphoma. There was an overrepresentation of cases with primary involvement of the gastrointestinal tract which was associated with exposure to these chemicals. The influence of previous diseases and socioeconomic factors was analysed through a supplementary questionnaire to the cases with HD and their matched controls. No differences were found in cases and controls for such variables except for tonsillectomy which was overrepresented among the cases as well as a history of previous duodenal or ventricular ulceration. These findings were, however, insignificant.     

Clonal T cell population in angioimmunoblastic lymphadenopathy and related lesions

The arrangements of the T cell receptor (TCR) beta genes were studied in lymph node specimens with the histological characteristics of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), AILD-like T cell lymphoma (AILD-T), T-zone lymphoma, or Lennert's lymphoma. Eight of 11 cases with AILD or AILD-T showed clonal rearrangements of TCR beta genes: all three AILD cases showed clonal rearrangements of TCR beta genes, while five of 8 AILD-T cases exhibited clonal rearrangement patterns. Malignant lymphoma evolved in one AILD case showed the same rearrangement band of TCR beta genes as its primary AILD lesion. The rearrangement of TCR beta genes was also observed in 2 out of 3 cases with T-zone lymphoma and 2 out of 2 cases with Lennert's lymphoma. None of the cases studied, except one AILD-T case, exhibited clonal rearrangements of immunoglobulin heavy chain genes. The results suggested that a significant proportion of AILD, AILD-T, T-zone lymphoma and Lennert's lymphoma cases are malignancies of peripheral T cell origin.     

Clinicopathological studies on coexisting gastric malignant lymphoma and gastric adenocarcinoma: report of four cases and review of the Japanese literature

Among 121 cases of primary gastric malignant lymphoma from 1962 to 1994 at the National Cancer Center Hospital, Tokyo, we found four cases (three males and one female) of adenocarcinoma coexisting in the stomach. The incidence of gastric malignant lymphoma together with gastric adenocarcinoma was 3.3%, suggesting that patients with lymphoma may have an increased incidence of gastric adenocarcinoma. A review of the Japanese literature revealed an additional 62 patients who developed coexisting gastric malignant lymphoma and adenocarcinoma. In the total series of 66 patients whose age and sex were recorded, there were 48 males with a mean age of 63.8 years and 18 females with a mean age of 58.6 years. Most adenocarcinomas were macroscopically early (76%) and of histologically differentiated type (75%). Conversely, 71% of lymphomas were of the advanced type macroscopically. The correct preoperative diagnoses were made in only 27% (16/59) of cases, when both tumors were located independently.      

Meningitis with Burkitt like B-cell lymphoma in HIV infection

Malignant lymphoma with meningeal involvement was detected in 7 patients with stage IV HIV infection. The diagnosis of lymphoma was made at a maximum of four months before discovery of meningeal involvement. In our seven cases the lymphoma was B-cell type, one case expressed Kappa chains, four cases demonstrated Lambda chains and in two cases differentiation was not possible. A review of findings in all HIV positive patients treated in the same period revealed 10 non-Hodgkin lymphomas of the B-cell type, though meningeal and cerebral involvement was observed only in B-cell lymphoma of the Burkitt type.     

Hodgkin's disease in patients with previous infectious mononucleosis.

Patients with a positive reaction to the Paul-Bunnell test in the period 1961-72 were identified at nine different laboratories in Norway and matched against cases of malignant lymphoma registered at the Cancer Registry of Norway in the period 1961-75. Among 5,840 patients having a positive Paul-Bunnell test a total of six developed malignant lymphoma, three of these more than 1 year after the positive Paul-Bunnell test. The expected number of malignant lymphoma was 2.04. Of the six lymphoma cases, five were classified as Hodgkin's disease (HD). The present investigation agrees well with the findings of other epidemiological studies. There seems to be a small excess in incidence of HD among patients with previous infectious mononucleosis (IM), but both diagnostic problems and possible confounding factors must be taken into account before a possible causal association is considered.     

Malignant change secondary to fibrous dysplasia

Background Malignant change in fibrous dysplasia (FD) is very rare. This study was carried out to establish some characteristic clinical information about this disorder. Methods Four cases with a malignant change in FD out of 128 cases with FD were surgically treated and followed up for a median period of 61.3 months. The mean age of the patients was 39.8 years. Clinical features, radiological findings, and the outcome were analyzed for each of the four cases. Results and conclusion The sites of the lesions were tibia (2 cases), femur (1 case), and rib (1 case). The forms of FD were monostotic in one case and polyostotic in three cases. Radiologically, plain films and computed tomography (CT) showed osteolytic lesions with poorly delineated margins within and/or near areas having a ground-glass appearance. In the osteolytic lesions, simple cystic changes associated with old FD could be excluded by enhanced magnetic resonance imaging (MRI). Histopathologically, two cases were osteosarcoma, one case was malignant fibrous histiocytoma (MFH), and one case was fibrosarcoma. The management of this disease should be decided according to the type of primary high-grade bone sarcoma. One patient, with MFH, was dead of lung metastasis 13 months after surgery. The others are alive without disease.     

Splenic lymphoproliferative disorders in human T lymphotropic virus type-I endemic area of japan: clinicopathological, immunohistochemical and genetic analysis of 27 cases

Primary splenic involvement in lymphoid neoplasms is rare and the clinicopathologic features of splenic lymphoma are not well described compared to nodal non-Hodgkin's lymphoma (NHL). Here we characterized splenic lymphomas in an human T lymphotropic virus type-I (HTLV-I) endemic area of Japan. To assess the pattern of splenic involvement and evaluate prognosis, we reviewed 27 specimens consisting of 26 splenectomies and one necropsy, which were classified using REAL classification. Cases were divided into primary splenic lymphoma in 11 patients and secondary in 16 patients. The incidence of primary splenic lymphoma was 0.3% (11 of approximately 4,000 malignant lymphomas). Primary splenic lymphomas included 7 diffuse large B cell lymphoma (DLBL), 2 follicular lymphomas (FL), and 1 each of splenic marginal zone lymphoma (SMZL) and anaplastic large cell lymphoma (ALCL). Secondary splenic lymphomas included 6 DLBL, 4 mantle cell lymphoma (MCL), 2 FL, 2 Hodgkin's disease (HD), 1 each of hairy cell leukemia and ALCL. Gross examination showed two patterns of splenic involvement; solid type (formation of large nodular mass, n=16) and disseminated type (multiple nodules with diffuse infiltration but no large nodular formation, n=10). The type could not be determined in one case. Most solid types were DLBL or FL, while MCL was of the disseminated type. Immunohistochemistry showed all but each 2 cases of ALCL and HD were of B lineage. Follow-up of 26 patients indicated that all but one patient with primary lymphoma were still alive (range, 1-89 months) and 8 of 15 patients with secondary lymphomas died due to the progression of malignant lymphoma; the survival rate at 2 years was 50% in these patients. No elevation of anti-HTLV-I antibody was found. In situ hybridization for Epstein-Barr virus (EBV) showed no reactivity of lymphoma cells, although a few small lymphocytes were positive for EBV. Hepatitis C virus was observed in 6 of 20 (30%) patients examined and 4 of 11 (36%) cases of primary splenic lymphoma. Our findings indicate that patients with primary splenic lymphoma have a favorable prognosis after splenectomy.     

Splenic Lymphoproliferative Disorders in Human T Lymphotropic Virus Type-I Endemic Area of Japan: Clinicopathological, Immunohistochemical and Genetic Analysis of 27 Cases

Primary splenic involvement in lymphoid neoplasms is rare and the clinicopathologic features of splenic lymphoma are not well described compared to nodal non-Hodgkin's lymphoma (NHL). Here we characterized splenic lymphomas in an human T lymphotropic virus type-I (HTLV-I) endemic area of Japan. To assess the pattern of splenic involvement and evaluate prognosis, we reviewed 27 specimens consisting of 26 splenectomies and one necropsy, which were classified using REAL classification. Cases were divided into primary splenic lymphoma in 11 patients and secondary in 16 patients. The incidence of primary splenic lymphoma was 0.3% (11 of approximately 4,000 malignant lymphomas). Primary splenic lymphomas included 7 diffuse large B cell lymphoma (DLBL), 2 follicular lymphomas (FL), and 1 each of splenic marginal zone lymphoma (SMZL) and anaplastic large cell lymphoma (ALCL). Secondary splenic lymphomas included 6 DLBL, 4 mantle cell lymphoma (MCL), 2 FL, 2 Hodgkin's disease (HD), 1 each of hairy cell leukemia and ALCL. Gross examination showed two patterns of splenic involvement; solid type (formation of large nodular mass, n = 16) and disseminated type (multiple nodules with diffuse infiltration but no large nodular formation, n = 10). The type could not be determined in one case. Most solid types were DLBL or FL, while MCL was of the disseminated type. Immunohistochemistry showed all but each 2 cases of ALCL and HD were of B lineage. Follow-up of 26 patients indicated that all but one patient with primary lymphoma were still alive (range, 1-89 months) and 8 of 15 patients with secondary lymphomas died due to the progression of malignant lymphoma; the survival rate at 2 years was 50% in these patients. No elevation of anti-HTLV-I antibody was found. In situ hybridization for Epstein-Barr virus (EBV) showed no reactivity of lymphoma cells, although a few small lymphocytes were positive for EBV. Hepatitis C virus was observed in 6 of 20 (30%) patients examined and 4 of 11 (36%) cases of primary splenic lymphoma. Our findings indicate that patients with primary splenic lymphoma have a favorable prognosis after splenectomy.     

Multicentric giant lymph node hyperplasia. A report of seven cases

Multicentric giant lymph node hyperplasia (MGLH) is a distinct lymphoproliferative disorder, which may terminate in malignant lymphoma. The clinical features and laboratory findings of seven cases are reported here. The histologic changes in lymph nodes were those of giant lymph node hyperplasia, plasma cell type. Immunoperoxidase staining showed intracytoplasmatic polyclonal immunoglobulins. Malignant lymphoma supervened in two cases, one of which was proved by autopsy; in the other there was transformation of a polyclonal gammopathy into a monoclonal one. Two of the patients also developed Kaposi's sarcoma.     

Malignant Lymphoma in Patients with the Wiskott-Aldrich Syndrome

The type and incidence of malignant lymphoma developing in patients with the Wiskott-Aldrich syndrome being followed at the National Cancer Institute (NCI) between the years 1966 and 1982 was evaluated. Histologic material from lymphoid tissue was available for review on 24 of the 50 Wiskott-Aldrich patients followed by the Metabolism Branch of the NCI. In 17 patients, specimens were obtained by biopsy performed for diagnosis of lymphoid mass lesions, and in 16 patients autopsy specimens were reviewed. In 9 of the 24 patients a diagnosis of malignant lymphoma was made. A distinct preponderance of non-Hodgkin s lymphoma (NHL) over Hodgkin's disease (HD) with a ratio 8:1 was observed, and the overall incidence of malignant lymphoma in all 50 patients was 18%. The most common histologic subtype of NHL was large cell immunoblastic. In all but one patient the diagnosis of lymphoma was made antemortem, most often presenting in extranodal sites or the brain. Involvement of peripheral lymph nodes was conspicuous by its absence. Immunoperoxidase staining for kappa and lambda chain immunoglobulin and lysozyme was negative in the four cases studied, failing to provide supportive evidence for a B-cell or true histiocytic origin for the tumor cells. Histologic subtypes of lymphoma commonly observed in childhood, such as Burkitt's lymphoma and lymphoblastic lymphoma, were not observed. Despite treatment with combination chemotherapy in some patients, there were no long-term remissions and median survival was less than one year following the diagnosis of lymphoma.