Lymphomas of the gastrointestinal tract: a study of 117 cases presenting with gastrointestinal disease.

A study was made of 117 patients who presented with gastrointestinal lymphoma. The occurrence was 48 in the stomach, 37 in the small intestine, 13 in the ileocecal region, two in the appendix and 11 in the large intestine. In six cases, multiple sites in the gastrointestinal tract were involved, but in five cases this appeared to be secondary to massive mesenteric or retroperitoneal lymph node disease. Using Rappaport's classification, diffuse histiocytic lymphoma was the most frequent histologic type and constituted 60% of the cases. Nodular lymphomas comprised 10% of the total, nodular poorly differentiated lymphocytic lymphoma forming the majority of this group. Ten of the lymphomas were undifferentiated, 5 of Burkitt's type and 5 non-Burkitt's type. Five were Mediterranean-type lymphomas associated with plasma cell infiltration of the adjacent mucosa, and only two cases of primary Hodgkin's disease were encountered. Two lymphomas could not be classified. Eight percent of the cases showed plasmacytoid changes and were classified as a distinct subgroup of the parent lymphoma rather than as examples of extramedullary plasmacytoma. Gastrointestinally lymphomas occurred most frequently during the fourth to seventh decades. However, nine lymphomas occurred in children younger than 16 years of age. In comparison to adults, the childhood lymphomas showed a number of notable differences with respect to sex distribution, site of involvement and histologic type. Information concerning the extent of the disease at the time of diagnosis was available in 75 cases. Of these, 49% of the lymphomas were confined to the affected viscus and 33% had associated regional lymph node involvement; the remaining 18% had mode widespread disease. In 44 patients information on the spread of disease was available and in 48% there was extra abdominal spread. Prognosis appeared to correlate best with the stage of the disease rather than the histologic type.     

Terminal deoxynucleotidyl transferase activity in lymphoma.

Terminal deoxynucleotidyl transferase (TdT) was estimated in the tissues of 42 patients with lymphoma, whose cells were also typed by the use of surface markers. Four of the 8 patients with T-cell lymphoma were TdT+ including patients whose lymph nodes showed an undifferentiated or poorly differentiated appearance. The TdT- T-cell lymphomas included cases with diffuse histiocytic Sezary cell, diffuse, poorly differentiated and angio-immunoblastic histology. The tissues of 31 patients with B-cell lymphoma were invariably TdT-, whether the histology was poorly differentiated, well differentiated, nodular, diffuse, histiocytic or Burkitt type, and including cases with about equal proportions of T and B cells, and those whose cells showed non-capping and capping surface immunoglobulin. Hodgkin's tissue was also invariably TdT-. We conclude that estimation of TdT in tissues of patients with malignant lymphoma may be a useful test in diagnosing the T-cell lymphoma, particularly in patients with tumours of undifferentiated or poorly differentiated histology.     

Immunologic phenotypes of diffuse, aggressive, non-Hodgkin's lymphomas. Correlation with clinical features

The immunologic phenotypes of 59 cases of diffuse, aggressive, non-Hodgkin's lymphomas were determined using a battery of immunologic and cytochemical techniques. Included were cases of diffuse, large cell "histiocytic," mixed cell, undifferentiated non-Burkitt's. Burkitt's lymphoma, lymphoblastic lymphoma, and mycosis fungoides/Sézary's syndrome were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunologic phenotypes. The immunotype could be determined in 57/59 (97%) cases tested: 31 of 59 cases (53%) were B-cell type, 25 of 59 (42%) were peripheral T-cell type, and one was true histiocytic. Two cases had no detectable markers and were called "null cell." This relatively high frequency of peripheral T-cell lymphomas in an American series previously has not been observed and may be a result of progressive improvements in immunologic techniques. Monoclonal anti-T cell antibody staining was performed in 11 T-cell cases and corroborated the findings using spontaneous E-rosette formation. Eight of the T-cell lymphomas had a helper cell phenotype whereas one had a suppressor cell phenotype and two could not be subclassified. All B-cell lymphomas in this series possessed monoclonal surface immunoglobulin detected by direct immunofluorescence of viable cells. Enzyme cytochemistry profiles only partially correlated with immunotype and were not believed to be helpful in the determination of specific phenotypes. There were no significant differences between the B-cell and T-cell diffuse aggressive lymphomas with respect to sex, constitutional symptoms, stages, sites of extranodal involvement, complete remission rate, or survival when they were studied prior to the initiation of aggressive therapy. Although immunotyping can be successfully performed in essentially all cases of diffuse, aggressive non-Hodgkin's lymphomas, to date, the authors have been unable to demonstrate that immunotype alone has an independent prognostic effect.     

Malignant lymphomas of the thyroid: a clinical pathologic study of 35 patients including ultrastructural observations.

The clinical and pathologic findings for 35 patients with malignant lymphoma presenting in the thyroid are reviewed. The lymphomas tended to occur in females with a median age of 65 years and clinically were manifested by a mass in the neck. The majority of patients were euthyroid and thyroid scans demonstrated cold nodules. In none of the patients was there clinical suspicion of lymphoma prior to surgery. Thirty-four of the cases were histiocytic lymphomas; the one exception; a patient with nodular poorly differentiated lymphocytic lymphoma, had histiocytic lymphoma in a subsequent biopsy of the soft tissues of the neck. Although classified as histiocytic, the lymphomas had the histologic and ultrastructural features of transformed lymphocytes or immunoblasts. Lending possible additional credence to the immunoblastic nature of these lymphomas was the histologic documentation of chronic lymphocytic thyroiditis in all 27 cases where residual thyroid parenchyma remained. This relationship suggests possible evolution of thyroid lymphomas from chronic lymphocytic thyroiditis and probably is analogous to the malignant lymphomas developing in other altered immune states, including Sjogren's syndrome. In the current study the overall 5-year survival was 54%. Patients under age 65, without local soft tissue extension or regional lymph node involvement, and with stage I disease survived the longest; a nodular histologic pattern also appeared to favorably influence the prognosis. Improved staging procedures and newer modes of therapy appear essential, particularly for those patients with clinical stage II disease and with local extension to soft tissues.     

Malignant lymphomas involving the prostate. A study of 13 cases

The clinical and pathologic findings in 13 cases of malignant lymphoma involving the prostate gland were reviewed. The lymphomas tended to occur in elderly men with a mean age of 60 years (range, 30-86 years) and were clinically manifested by prostatic enlargement with urinary obstruction. In only one of the patients was there clinical suspicion of lymphoma before surgery. Seven patients had primary extranodal lymphoma of the prostate, with a variety of histologic subtypes, including small cell lymphocytic (one patient), diffuse small cleaved cell (two patients), diffuse mixed small and large cell (two patients), diffuse large non-cleaved cell (one patient), and high-grade diffuse small non-cleaved cell (undifferentiated non-Burkitt's) (one patient). At the time of presentation, none of these patients had hepatosplenomegaly, inguinal lymphadenopathy, abnormal complete blood counts, or elevated serum acid phosphatase levels. Six other patients with previously documented malignant lymphoma at other sites had prostatic involvement 2 to 60 months (mean, 14 months) after the primary diagnosis. Histologically, these secondary prostatic lymphomas included diffuse small cleaved cell (two patients), diffuse mixed small and large cell (one patient), diffuse large non-cleaved cell (two patients), and large cell immunoblastic, polymorphous type (T-cell by immunotyping) (one patient). The mean survival was 14 months for all patients (range, 2-44 months), with no apparent difference between primary and secondary involvement. One patient remains alive 44 months after secondary prostatic involvement with diffuse large non-cleaved cell lymphoma. Although malignant lymphomas involving the prostate are rare, they should be included in the differential diagnosis of lower urinary tract obstruction, particularly in patients with a previous history of lymphoma.     

Clinical features and treatment of childhood malignant lymphoma in Uganda

A series of 66 patients with Burkitt's lymphoma or childhood lymphoma of the histiocytic or lymphoblastic type has been analysed. The six patients with histiocytic lymphomas had clinical features, response to therapy and survival rates which clearly distinguished this group from Burkitt's lymphoma. Of the six patients with lymphoblastic lymphomas, however, three presented with clinical features indistinguishable from Burkitt's lymphoma while two had facial tumors which showed atypical features. The response to chemotherapy with CTX was more favorable in the lymphoblastic than in the histiocytic group, and the survival rate in this small number of patients falls midway between those of histiocytic lymphoma and Burkitt's lymphoma. Thus, the clinical evaluation of Ugandan children with lymphoblastic lymphoma did not clearly distinguish this group from patients with Burkitt's lymphoma, and casts some doubt on the use of clinical features or response to therapy as diagnostic criteria.     

B-cell lymphomas morphologically resembling T-cell lymphomas

Seven cases of B-cell lymphoma that morphologically resembled T-cell lymphoma are described. These cases are of four morphologic types: atypical poorly differentiated lymphocytic lymphoma (PDLL) with convoluted nuclei, "Lennert's" lymphoma, mixed lymphocytic-"histiocytic" lymphoma with large variation in size of abnormal cells, and "histiocytic" lymphoma with large multilobed nuclei. These cases add further support to the belief that morphologic criteria alone are not sufficient for accurate immunologic classification of the malignant lymphomas since they may represent a distinct clinicopathologic entity.     

Non-Hodgkin's lymphoma in bone. Pathologic and radiologic features with clinical correlates

Thirty-seven lymphomas of bone were studied, including 33 diffuse large cell lymphomas, three undifferentiated (small noncleaved cell) lymphomas, and one well-differentiated (small) lymphocytic lymphoma. The large cell lymphomas were subclassified as large cleaved, large noncleaved, multilobated cell, and immunoblastic sarcoma (large cell lymphoma, immunoblastic type). Eleven of 26 large cell lymphoma patients with adequate follow-up were long-term survivors (free of disease for more than 5 years). Nineteen of the 33 large cell lymphomas were localized to one bone. The stage and histologic pattern significantly correlated with long-term survival among large cell lymphomas. Seventy-three percent of patients with localized lymphoma were long-term survivors, in contrast to 9% of those with disseminated disease. Sixty-seven percent of patients with large cleaved and multilobated cell lymphoma were long-term survivors, but only 21% of those with large noncleaved cell and immunoblastic sarcoma were. The tumors had a blastic, lytic, or mixed radiographic appearance and had either sclerotic, lytic, or permeative borders; none of the radiologic findings were diagnostically useful.     

Surface markers and functional properties of non-Hodgkin's lymphoma cells in relation to histology.

Cells from 32 adult patients with non-Hodgkin's lymphoma were studied with respect to surface markers and functional properties in short-term culture. Twenty-six lymphomas were of B-cell origin, including all nodular and diffuse lymphocytic lymphomas. Three tumors were of T-cell origin (one histiocytic lymphoma and two undifferentiated lymphomas). In the remaining three cases (histiocytic lymphomas) the immunological nature of the tumor cells could not be determined. All reactivity to mitogenic stimuli of cells from B-cell lymphomas was due to residual normal T cells. In follicular lymphocytic lymphomas more reactive T cells prevailed among the malignant B cells than in diffuse lymphocytic lymphomas. Heterogeneity among B-cell lymphomas was indicated by differences in intensity of fluorescence with anti-Ig reagents and in stimulatory capacity in mixed lymphocyte culture. T-cell lymphomas were characterized by high percentages of T cells together with impaired responses to stimuli. The results of immunological studies correlated well with the histological classifications of Rappaport, Lukes and Lennert.     

Radiation therapy of Waldeyer's ring lymphoma

Forty-nine patients with biopsy-proven Waldeyer's ring lymphoma were treated with radiation therapy between 1968 and 1979; 45 to 50 Gy were given to Waldeyer's ring structures with a 5- to 10-Gy boost to the primary site. Uninvolved low cervical nodes received 40 to 50 Gy. Chemotherapy was reserved for treatment failures. Actuarial 5-year survival was 53%, disease-free survival was 48%, and local control was 98%. Patients with Stage I disease fared better than patients with Stage II disease, and unilateral adenopathy conferred a better prognosis than bilateral adenopathy. When classified by the Rappaport system, nodular lymphomas had a better prognosis than diffuse lymphomas, and of the diffuse lymphomas, histiocytic lymphoma was a more lethal disease than lymphocytic lymphoma. Patients with diffuse undifferentiated lymphomas in the Rappaport system, or high-grade lymphomas in the Working Formulation, fared poorly. Most relapses were systemic, and actuarial 5-year survival after salvage was only 20%. A logical approach to the treatment of this disease can be based on these prognostic features.     

Clinico-pathologic studies on 143 cases of tonsillar malignancies with special reference to lymphomas]

143 cases of tonsillar malignancies consulted or treated in our hospital during the past 33 years (1958-1991) were studied morphologically and histochemically. There were 126 non-Hodgkin's lymphomas (NHL), 14 squamous cell carcinomas and one each of mucoepidermoid carcinoma, malignant melanoma and histiocytic lymphoma. The results showed that: 1. The ratio of peripheral T-cell and B-cell lymphoma was high (2.08:1), of which the reason is unexplained, 2. Many tonsillar NHLs had been misdiagnosed as undifferentiated carcinomas, poorly differentiated carcinomas or reticular cell sarcomas in the past, and 3. Most of the B-cell lymphomas belong to the high grade malignant large cell lymphomas, like the large non-cleaved and immunoblastic type. These findings are different from what is generally believed and known.     

Primary non-Hodgkin malignant lymphoma of the breast. An immunohistochemical study of seven patients and literature review of 152 patients with breast lymphoma in Japan.

BACKGROUND. The breast is rarely a primary site for extranodal malignant lymphoma. Most reported primary non-Hodgkin malignant lymphomas of the breast (PBL) are of B-cell phenotype. METHODS. Histologic and immunohistochemical analyses of seven patients with PBL and a statistical analysis of 152 patients with PBL reported in the Japanese literature were performed. RESULTS. Malignant lymphoma could not be predicted preoperatively with clinical and radiologic findings; breast carcinoma, fibroadenoma, and phyllodes tumor were the preoperative diagnoses. All patients were women; they ranged in age from 31 to 80 years (mean, 57.6 years). The right breast was involved initially in five patients. In four, only the breast was involved (Stage I), whereas in three, the ipsilateral axillary lymph nodes (Stage II) were involved at diagnosis. According to the Working Formulation, all patients belonged to the intermediate grade and were classified as having diffuse large cell (five patients) or mixed (two patients) lymphoma. Immunophenotypic analysis revealed that all patients had B-cell lymphoma. No patients had lymphoepithelial lesions, which is the characteristic feature in categorizing a lymphoma as a mucosa-associated lymphoid tissue (MALT) lymphoma. A statistical analysis of the patient reported in the Japanese literature has divided PBL into two types: a bilateral type that affects younger women and a unilateral type that has a broad age distribution, but preponderantly occurs in older women. The age and stage at diagnosis were significant prognostic factors in predicting the survival time, but the location and size of the tumor at initial presentation, histopathologic type, terminal leukemic manifestation, and treatment modality were not. CONCLUSIONS. This study indicates that most PBL are diffuse large cell lymphoma of B-cell phenotype and that the age and stage at diagnosis are significant prognostic factors.     

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.     

Histiocytic neoplasias: immunohistochemical evaluation of their frequencies among malignant lymphoma and related conditions in Japan

Through histologic review of 1,766 cases with malignant lymphoma and related conditions, 35 cases (2%) were selected as probable histiocytic neoplasias. Proliferating cells in these cases had voluminous, granulated cytoplasm, and round to irregularly shaped nuclei often with bi- or multinucleated forms showing monomorphous or polymorphous proliferation accompanying small lymphocytes, plasma cells, and, less frequently, eosinophils. Cases showing proliferation of convoluted cells with numerous benign-appearing histiocytes or large cells with clear cytoplasm were excluded under a diagnosis of T-cell lymphoma. To evaluate the immunologic character of proliferating cells, immunohistochemistry using antibodies Mx-Pan B, MB-1, MT-1, UCHL-1, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 alpha, S-100 beta, Leu M1, epithelial membrane antigen, and Ki-1 were carried out in 23 cases. Naphthol-ASD-chloracetate reaction and toluidine blue stain were also performed. These procedures revealed that 12 cases (52%) were B-cell type, three cases (13%) T-cell type, six cases (26%) true histiocytic type, and two cases null type. Therefore, the frequency of cases with true histiocytic neoplasias among cases with malignant lymphoma and related conditions in Japan may be 0.5%.     

Primary lymphoma of the breast: ultrastructural study of two cases.

Two cases of primary non-Hodgkin's lymphomas of the breast were studied with light and electron microscopy. By light microscopy, according to Rappaport's classification, one was a poorly differentiated lymphocytic lymphoma, the other a diffuse histiocytic lymphoma. However, the ultrastructural features of the latter were more consistent with transformed lymphocytes. The differential diagnosis with medullary and poorly differentiated carcinomas of the breast is discussed. The first case had rapid dissemination as did most of the cases reported in the literature.     

Pathology of primary non-Hodgkin's lymphoma of bone

35 cases of primary non-Hodgkin's lymphoma (NHL) of bone are analysed. According to the diagnostic criteria of malignant lymphoma introduced at the National Conference on Lymphoma, they were divided into 3 groups: B cell derivative, T cell derivative and histiocytic derivative lymphomas. NHL of the bone was all of diffuse infiltration type, in which the incidence of T-cell and histiocytic derivative lymphomas was relatively frequent. X-ray changes and frequent complications of pathologic fracture in the tumor might be explained by the penetrating and osteolytic growth and direct morphologic osteolytic action of the tumor cells. But local fibrosis is more commonly found, on the basis of which reactive osseous hyperplasia is formed. Sometimes there are more macrophages and lymphocytes admixed around the tumor. It shows the immune reaction of the organism to the tumor.     

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.     

Malignant Lymphomas in Korea

A retrospective histological study based on biopsy materialof 341 cases of malignant lymphoma diagnosed at the Departmentof Pathology of the Seoul National University from 1976 through1983 was conducted, to reveal some characteristics of malignantlymphomas occurring in Korea. Malignant lymphoma was the seventh most common malignant tumor(4.03%) among Koreans. Non-Hodgkin's lymphoma predominated overHodgkin's disease, accounting for 87% of all malignant lymphomas.Follicular lymphoma was rarely seen in Korea (3%), and amongtypes of non-Hodgkin's lymphoma the diffuse histiocytic type(57%) and the poorly differentiated lymphocytic type (26%) ofRappaport were common. Follicular center cell lymphomas (Lukes-Collins)were most commonly seen, whereas T-cell lymphoma was found inapproximately 10% of the non-Hodgkin's lymphomas. Not a singlecase of pleomorphic adult T-cell lymphoma was encountered inthis series. Among sub types of Hodgkin's disease the nodularsclerosis type was particularly rare, comprising only 15% ofthe Hodgkin's disease cases.     

Nodular lymphocytic lymphoma eventuating into diffuse histiocytic lymphoma: immunoperoxidase demonstration of monoclonality.

The patient described here had a nodular, poorly differentiated lymphocytic lymphoma associated with a serum monoclonal protein, IgG lambda. Following a three year period of radiation-induced clinical remission she developed generalized diffuse histiocytic lymphoma. Direct immunoperoxidase staining of the tissue sections demonstrated that the neoplastic cells of each biopsy only contained IgG lambda immunoglobulin, identical to the serum monoclonal protein. This is presumptive evidence that these two histopathologically distinctive malignant lymphomas, occurring consecutively in the same patient, were responsible for the synthesis and secretion of the same serum M component. This strongly suggests that both lymphoid neoplasms arose from the same malignant clone. The results 1) confirm the light microscopic observation that nodular lymphocytic lymphoma may progress to diffuse histiocytic lymphoma and 2) offer further evidence that histiocytic lymphomas arising in patients with previous B cell malignancies are most probably related to the original B cell proliferation and do not represent the emergence of a second, separate malignant clone.