Yasuo Hosomura

Immunological abnormalities in splenic marginal zone cell lymphoma

The clinical features of patients with splenic marginal zone cell lymphoma (SMZCL) have rarely been reported. In the present study, immunological abnormalities, particularly hematological abnormalities, observed in SMZCL were described. Autoimmune hemolytic anemia, immune thrombocytopenia, and appearance of lupus anticoagulant were observed in 2 of 3 patients with SMZCL. Other abnormal data including monoclonal gammopathy and cold agglutinin were also observed in 2 of the 3 patients. Immunological abnormalities may be characteristic complications in patients with SMZCL and must be followed carefully, since they may be a reliable marker of this type of lymphoma activity. Am. J. Hematol. 56:173–178, 1997.

Inflammatory Pseudotumor of Lymph Nodes: Clinicopathologic and Immunohistological Study of 11 Japanese Cases

We report 11 Japanese cases of inflammatory pseudotumor (IPT) of the lymph node. There were 7 males and 4 females with ages ranging from 5 to 68 years (median; 48). Only 2 patients had systemic lymphadenopathy, and all others had involvement of only 1 lymph node group. Constitutional symptoms such as fever were present in 8 patients and laboratory abnormalities were detected in 5. All patients recovered and were alive and well after 2 to 180 months (median; 32 months). Histologically, the process mainly involved the connective tissue framework of the lymph node, secondarily spreading into the lymph node parenchyma and the perinodal tissue. It was characterized by a storiform growth pattern of myofibroblasts, marked vascularity with associated vascular lesions, and a polymorphous reactive cellular infiltrate in a collagen-rich stroma. An immunohistochemical study revealed numerous myofibroblasts, histiocytes, and vascular endothelial cells expressing vascular endothelial growth factor (VEGF) in 6 cases. It was suggested that VEGF may be involved, in part, in the induction of the angiogenesis of IPT. Moreover, the present study indicates that follicular dendritic cell sarcoma, nasal T/natural killer cell lymphoma, and anaplastic large cell lymphoma should be added to the differential diagnosis from IPT of the lymph node.

Small ileal neurofibroma causing intussusception in a non-neurofibromatosis patient

Neurofibromas in the small intestine are usually accompanied by von Recklinghausens disease (neurofibromatosis), and usually originate in the intramuscular plexus of Auerbach. We present here a solitary neurofibroma, which caused an ileocolic intussusception, originating in the submucosal plexus of Meissner in a non-neurofibromatosis patient. To our knowledge, there is no previous report of a neurofibroma originating in the plexus of Meissner. This condition was clearly confirmed by macroscopic and microscopic evaluation.

Primary malignant lymphoma of the intestine: Clinicopathologic and immunohistochemical studies of 39 cases

Clinicopathologic and immunohistochemical features in 39 cases of primary intestinal non‐Hodgkins lymphoma (NHL) in Japanese patients were studied. Only resection materials in stage IE and IIE‐1 were included in this study because of the certainty that the intestine was the primary site of the lymphoma. The updated Kiel classification was used to classify NHL Histologically, only two cases (5.1%) were follicular lymphomas, and the others were diffuse lymphomas. Twenty‐eight patients (71.8%) had high‐grade NHL and 11 (28.2%) had low‐grade NHL. Twenty (71.4%) of the 28 high‐grade NHL were centroblastic lymphomas, and 14 (70.0%) of these 20 cases of centroblastic lymphoma were the polymorphic variant. Ten (90.9%) of the 11 low‐grade NHL were low‐grade mucosa‐associated lymphoid tissue (MALT) lymphomas. Macroscopically, 18 patients had polypoid masses, 17 ulcerative tumors and four had diffusely infiltrating NHL. Seven of the 10 low‐grade MALT lymphomas were polypoid masses. Immunohistochemically, 35 lesions (89.7%) were of the B cell phenotype and three (7.7%) were of the T cell phenotype. In the remaining case, the cell lineage could not be determined. No lesions were considered to be Of histio‐cytic origin. The 5 year survival rate for high‐grade B cell lymphomas was poorer than for low‐grade B cell lymphomas, and the present study indicated that the histological grade of the intestinal B cell lymphomas was a prognostically significant factor.

Reactive Proliferative Lesions in Lymph Nodes from Rheumatoid Arthritis Patients

In 22 cases of rheumatoid arthritis (RA), including 4 cases of malignant RA (MRA), reactive proliferative lymph node lesions were studied clinicopathologically and immunohis‐tochemically. This series included 5 males and 17 females. The period between disease onset and lymph node biopsy ranged from 3 months to 41 years. Generalized lymphadenopathy was noted in 13 cases and constitutional symptoms in 8. The histological findings characteristic of RA were 1) follicular hyperplasia with active germinal centers and 2) polyclonal plasma cell infiltration in the interfollicular area. Studies of intracytoplasmic immunoglobulin showed that γ‐heavy chain‐expressing plasma cells were a major component in the interfollicular area in 17 RA cases. However, in 4 MRA cases, a prominent increase of μ chain‐expressing plasma cells was recognized in the same area. In the 3 cases for which fresh tissue sections were stained with monoclonal antibodies against lymphocytes, we found that the majority of T cells in the interfollicular area had helper/inducer markers. The identical locations of the T cell population and plasma cells indicated that both played a role in the proliferation and/or differentiation of B cells in lymph nodes in RA.

Florid reactive follicular hyperplasia in elderly patients. A clinicopathological study of 23 cases.

Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in elderly patients requiring biopsy is a relatively uncommon phenomenon as compared with younger age groups. We experienced 23 patients, aged 60 years or more, from whom the biopsied lymph node specimens histologically showed inappropriate FRFH for their age, in the period between 1982 and 1996. These cases were morphologically subdivided into three groups, FRFH with interfollicular plasmacytosis, that with progressive transformation of germinal center, and FRFH without additional specific findings. FRFH with interfollicular plasmacytosis were observed in 11 cases, all of whom were accompanied with several immunological abnormalities (six with rheumatoid arthritis, three with multicentric Castlemans disease and one each with myoepithelial sialoadenitis and autoimmune hemolytic anemia). Three men with uncertain etiology exhibited an unusual histology of progressive transformed germinal centers which were clinically characterized by a bulky neck mass. Among the nine cases with nonspecific FRFH, only four had a specific etiology (one each with adult onset Stills disease, chronic sinusitis, Epstein-Barr virus infection and infectious lateral cervical cyst), while the other five with unknown etiology showed abnormal laboratory findings suggestive of an abnormal humoral immune response, i.e. hypergammaglobulinemia and seropositivities for some autoantibodies. None of our patients developed malignant lymphoma during the follow-up period. Of note, 16 (70%) of the 23 cases were found to be associated with various types of imbalances of the immune system, some of which appeared to be currently ill-defined as clinicopathological entities that were simply categorized as autoimmune disease.

Malignant lymphoma of Waldeyer's ring. A histological and immunohistochemical study.

The histopathological and immunohistological features of non‐Hodgkins lymphoma limited to the Waldeyers ring were studied in 22 Japanese patients using a panel of T‐ and B‐cell markers on paraffin‐embedded sections. All cases showed a diffuse growth pattern. Twenty cases were B‐cell lymphomas and two were T‐cell lymphomas. In contrast to the primary malignant lymphomas of the nasal cavity and paranasal sinuses, in which T‐cell neoplasms are more frequently seen, the majority of the primary Waldeyers ring lymphomas were B‐cell neoplasms. Sixteen of the 20 cases of B‐cell lymphoma were centroblastic lymphomas, and the monomorphic variant comprised the majority of these; the other three B‐cell lymphomas were immunocytomas. Two of the T‐cell lymphomas showed morphological features of angiocentric lymphomas.

Centroblastic and Centroblastic/Centrocytic Lymphoma Associated with a Prominent Epithelioid Granulomatous Response: a Clinicopathologic Study of 50 Cases

A minority of centroblastic and centroblastic/centrocytic cell lymphomas are accompanied by a prominent epithelioid cell response and were suggested to be a distinct variant of B-cell lymphoma of germinal center cell origin. To confirm the clinicopathologic significance of these mainly large B-cell lymphomas with an epithelioid cell response (LBCL-ER), we reviewed 50 patients with LBCL-ER and compared the results with those of 167 other diffuse large B-cell lymphomas (DLBCL) and 94 follicular lymphomas (FL) without epithelioid response. The patients with LBCL-ER showed a higher age distribution (median 71, P = .03), a female predominance (M:F = 18:32, P = .001) and less frequent involvement of extranodal sites >1 (P = .004) compared with those with DLBCL, and presented with a bulky mass of the affected lymph nodes in 54% of cases. They were also older (P = .0006) and more associated with the aggressive clinical factors such as serum LDH level and International Prognostic Index score than those with FL. Histologically, nine cases (18%) partially showed a follicular growth pattern, and the others (82%) were occupied by a diffuse growth pattern. The epithelioid cells were accumulated in large demarcated masses, partially imparting a lymphoepithelioid (Lennert) lymphoma-like appearance to some portions of the lesions in every case. Immunohistochemically, LBCR-ER was positive for CD20 in every case, CD10 in 43% of the cases, and BCL-2 in 56%. None of the tumor cells in the 40 cases tested expressed CD5 antigen. Immunostaining also often highlighted the remnants of the follicular dendritic cell network. The BCL-2 gene rearrangement was detected in only 19% of the cases examined. The survival curve of the cases of LBCL-ER was almost identical with that of DLBCL and was significantly inferior to that of FL. The centroblastic and centroblastic/centrocytic lymphoma with an epithelioid cell response may be regarded as the morphologic variant of DLBCL preferentially arising in the aged population and reflecting the disease progression of FL.

Malignant lymphomas of the nasal cavity and paranasal sinuses. A clinicopathologic and immunohistochemical study.

The clinicopathologic and immunohistological features of 20 Japanese patients with non‐Hodgkins lymphomas (NHLs) limited to the sinonasal area were studied using a broad panel of T‐ and B cell markers on paraffin‐embedded and fresh frozen tissue. All cases showed a diffuse growth pattern. Nine cases were B cell lymphomas (immunoblas‐tic n = 4, centroblastic n = 3, immunocytoma n = l, centrocytic n = l), and nine were T‐cell lymphomas (pleomorphic medium and large cell n = 8, angioimmuno‐blastic n = 1). In two cases, the cell lineage could not be determined. No morphologic features of angiocentric/an‐giodestructive lymphoproliferative lesions or lymphoepithe‐lial lesions in ductal or glandular epithelium were seen in our series. Eight (89%) of the nine T‐ cell tumors and four(44%) of the nine B ‐ cell neoplasms involved both the nasal cavity and paranasal sinuses. Six of the nine T ‐ cell neoplasms showed a clinical presentation of rhinitis, whereas all of the B ‐ cell neoplasms showed tumor masses in the nasal cavity and/or paranasal sinuses. The two‐year survival rate for T cell lymphomas was poorer than that for B‐cell lymphomas. The five‐year survival of patients with NHLs involving both the nasal cavity and paranasal sinuses was also poorer than that of patients in whom NHLs were limited to the nasal cavity. Acta Pathol Jpn 42:333–338, 1992.

Centroblastic and centroblastic-centrocytic lymphomas associated with prominent epithelioid granulomatous response without plasma cell differentiation: a clinicopathologic study of 12 cases.

To clarify the clinicopathologic features of B-cell lymphoma associated with prominent epithelioid granulomatous responses other than immunocytomas, 12 patients were studied. There were six men and six women. The lymphoma generally affected elderly patients (median age, 58.5 years) and was mostly nodal in origin. Seven of the 12 patients had a localized lesion (stage I or II), and five had an advanced lesion (stage III or IV). Histologically, four patients showed a follicular growth pattern and eight a diffuse growth pattern. Based on the updated Kiel classification, nine patients showed centroblastic lymphomas, and three showed centroblastic-centrocytic lymphomas. The epithelioid cells were accumulated in large, poorly demarcated masses. Trabecular fibrosis compartmentalized in the lymph nodes, producing a vague nodular pattern in low-power fields. Immunohistochemical studies of the tumor cells revealed positive membrane staining with L26 in all 12 patients and with LN-1 antibody in 9 of 10 patients. Expression of the bcl-2 protein was present in all seven patients tested. Genotypic investigation exhibited germline configuration of the immunoglobulin heavy chain gene, the T-cell receptor beta-chain gene and the bcl-2 gene in all three patients investigated. By in situ hybridization, Epstein-Barr virus genomes were detected in only a few tumor cells in three of the patients tested. This study indicated that most, if not all, of the B-cell lymphomas with prominent epithelioid granulomatous responses other than immunocytoma were of follicular center cell origin.