Hideaki Itoh

Systemic lupus erythematosus (SLE) lymphadenopathy presenting with histopathologic features of Castleman' disease: a clinicopathologic study of five cases.

Lymph node enlargement is common in active systemic lupus erythematosus (SLE), a disease characterized by well defined clinical criteria. Although numerous reports have described the characteristic histology of SLE lymphadenopathy to include necrotizing lesions and hematoxylin bodies, no detailed description has examined the histopathologic features that are similar to Castlemans disease (CD) in SLE patients. In this report, we describe the clinicopathologic findings of CD-like peripheral lymphadenopathy, which was identified in five (26%) of 19 SLE patients. These five patients were all female with an age range of 24 to 44 years, and four of them presented with multicentric lymphadenopathy. They also had systemic symptoms and abnormal laboratory findings, indicating active disease, although two patients had not fulfilled the diagnostic criteria of SLE at the initial disease. The size of the enlarged lymph nodes seldom exceeded 2.0 cm in diameter, and biopsies revealed histopathologic features similar to CD, of intermediate type in three patients and hyaline vascular type in two according to the classification of Flendrig [7]. Immunohistochemical studies demonstrated polyclonal plasma cell populations in all five cases. Epstein-Barr virus genomes were detected in the small lymphocytes of two of the three cases examined by in situ hybridization studies. Recently, the histopathologic findings of CD have been associated with a disrupted immune response, and the present data suggest that SLE should be listed as one of the diseases showing the histopathologic features similar to CD.

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.

Occurrence of Monocytoid B-cells in Reactive Lymph Node Lesions

Benign monocytoid B-cells are a peculiar subset of B-cells. They are closely related to marginal zone B-lymphocytes, show cytological diversity and may be recognized in a variety of reactive lymph node conditions. To analyze the incidence, cytological spectrum and phenotypic features of benign monocytoid B-cells, we investigated a series of 301 consecutively biopsied and unselected cases of reactive lymph node change from 1988 and 1995. A monocytoid B-cell reaction was identified in 46 (15%) cases and could be cytologically subclassified into two groups: 31 (67%) cases with common-type cells and 15 (33%) cases with large, transformed cells, according to the description by Plank et al. [19]. These reactions were regularly associated with follicular hyperplasia (95%) and were part of an epithelioid cell response in 24 cases (50%). Immunohistologically, both types of benign monocytoid B-cells were negative for bcl-2 protein expression, which was in contrast to the bcl-2 positive reaction in marginal zone B-lymphocytes and their neoplastic counterpart in monocytoid B-cell lymphoma. An association of Epstein-Barr virus (EBV) with monocytoid B-cells was investigated by in situ-hybridization. EBV genomes were detected in five (15%) of 31 cases tested. In each of these five cases, positive cells were represented in both high and low numbers. The morphologic features of the EBV-positive cells were not consistent with monocytoid B-cells, but rather with medium-sized to large lymphoid cells. It appeared that the occurrence of monocytoid B-cell reaction in reactive lymph node lesions was not related to EBV infection in the majority of cases.

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.

Suppurative Lesions without Prominent Epithelioid Cell Response in Abscess-forming Granulomatous Lymphadenitis

To clarify the clinicopathological significance of the suppurative lesions without an epithelioid granulomatous response (SLs without Ep) in lymph nodes and their relationship to abscess-forming granulomatous lymphadenitis (AGL) and cat scratch disease (CSD), 10 cases were assessed clinicopathologically and immunohistologically. SLs without Ep were located in the subcapsular sinus, paracortical area and medullary cords, but not in the germinal centers. The microabscesses were surrounded by collections of monocytoid B-lymphocytes (MBLs), histiocytes without epithelioid features, neutrophils, small lymphocytes and small numbers of plasma cells. The majority of the MBLs seen in the SLs without Ep were of the large cell type. The histological triad of toxoplasmic lymphadenitis, i.e., reactive follicular hyperplasia, small clusters of epithelioid cells and aggregates of MBLs, were also seen in all cases. Some of the clinical and pathological findings in our 10 cases were characteristic of CSD, i.e., (1) cat exposure before the lymphadenopathy was in four of the 10 cases, (2) occurrence in autumn and winter months in all cases, (3) typical suppurative granulomas surrounded by palisaded epithelioid cells were in four of the 10 cases, and (4) Warthin-Starry silver stain-positive bacteria were detected in seven of the 10 cases. The results of our study suggest that SLs without Ep are an early stage of CSD.

Imprint cytology of cat scratch disease

The cytologic features of cat scratch disease (CSD) from eight cases in imprint smears are presented. All patients were clinicopathologically diagnosed as CSD as follows: 1) a history of animal exposure was recorded 2 to 4 weeks before lymphadenopathy; 2) the disease occurred in the autumn and winter months; 3) a characteristic histopathology in the biopsied lymph node specimens was observed; and 4) Warthin‐Starry silver stain‐positive bacteria were detected in four of the seven cases examined. The characteristic cytologic finding was the presence of confluent epithelioid cells with nearby and central scatterjng of neutrophils against a background of polymorphic inflammatory cells. Furthermore, a varying number of medium‐sized to large lymphoid cells with an appearance suggestive of monocytoid B lymphocytes (MBLs) were noted to be associated with the epithelioid cells. These cytologic findings closely paralleled the histologic patterns of epithelioid cell granulomas, with and without MBLs, which we have previously reported are probably associated with the disease.

Monocytoid B Lymphocytes and Epithelioid Cell Clusters in Abscess‐forming Granulomatous Lymphadenitis With Special Reference to Cat Scratch Disease

In order to clarify the appearance of monocytoid B lymphocytes (MBLs) in abscess‐forming granulomatous lymphadenitis (AGL) and the relation between AGL and cat‐scratch disease (CSD), 48 cases of AGL were studied histologically. MBLs were present in about 50% of AGL cases. Warthin Starry (WS) silver stain‐positive bacteria, which are the causative agent of CSD, were present in 52.4% of AGL cases with MBLs and 59.2% of AGL cases without MBLs. The appearance of MBLs in AGL was not related to various clinical features, including disease interval from initial lymphadenopathy to lymph node biopsy. Histologically, epithelioid cell clusters appeared in about 70% of MBL positive AGL cases, but were not observed in MBL negative AGL. Therefore, a close interaction between MBLs and epithelioid cells in AGL is suggested, and we emphasize that the histological features of some AGL cases resemble those of toxoplasmic lymphadenitis.

Imprint cytology of large b-cell lymphoma with high content of epithelioid cells. A report of two cases

An association of epithelioid cell reaction in follicular center cell lymphomas seems to be a rare phenomenon. The cytological features of this type of B-cell lymphoma from two patients are presented. In both cases, immunohistochemistry applied to paraffin sections revealed reactivity of tumor cells for CD10, 20 and 79a. The first patient, a 77-year-old male, presented with bilateral inguinal bulky masses. The second patient, a 76-year-old female, revealed left supraclavicular bulky masses. Imprint cytological specimens of these two cases showed large lymphoid cells interspersed with epithelioid histiocytes, which were present in small aggregated clusters or in isolated forms. Most tumor cells showed centroblastic morphology, whereas the minority of them looked like immunoblasts. Occasionally, a monotonous proliferation of these large atypical blastic cells was also detected. On the other hand, in some parts of the imprint specimens, numerous epithelioid cells obscured the underlining tumor cells. Reactive cells other than epithelioid cells were not prominent. These cytologic features closely resembled the histologic patterns of this rare follicular center cell lymphoma. Careful examination of the cytological specimens is needed to detect the monotonous proliferation of tumor cells to establish the diagnosis of malignant lymphoma.

Hepatocellular Carcinoma Associated with Extrahepatic Primary Malignant Neoplasms

BackgroundWe studied hepatocellular carcinoma (HCC) with extrahepatic primary malignant neoplasms (EPMNs) and investigated its clinical and pathologic relevance.MethodData from autopsies performed during the last 10 years (January 1985 to December 1994) on 146 patients with HCC were analyzed at Maebashi Red Cross Hospital. The 146 patients consisted of 116 men and 30 women ranging in age from 38 to 87 years at the time of death.ResultsEPMNs were found in 21 patients: in the large bowel (6 cases), stomach (4 cases), thyroid (2 cases), urinary bladder (2 cases), small intestine (2 case), liver (1 case) and 1 case in the lung, pancreas, prostate, and breast, respectively. One patient had a malignant lymphoma in the small intestine. Ten EPMNs (47.6%) were latent or found at autopsy. The frequency of blood transfusion was significantly higher in the patients with EPMNs than in those without EPMNs. Those with EPMNs tended to be older and more likely to be male. Sixteen of the 21 patients died of liver-related causes. Two patients died of a second cancer, and 3 died of reasons other than malignancy, such as brain hemorrhage and pneumonia.ConclusionFully 14.4% of patients whose autopsies showed HCC had EPMNs. Survival from the time of diagnosis of HCC did not differ significantly in the patients with EPMNs. These observations suggest that EPMNs did not change the prognosis of these patients with HCC, even when their EPMNs had been detected and treated early.

Cytologic features of mucosa-associated lymphoid tissue(MALT) lymphoma arising from parotid glands.

耳下腺に発生した低悪性度mucosa-associated lymphoid tissue (MALT) リンパ腫の2例の捺印細胞所見について報告した. 1例では中型の細胞が主として出現していた. 中型の細胞には2種類がみられた. ひとつは淡明な細胞質と, くびれた核を有していた (centrocyte-like cells). もうひとつはMay-Giemsa (M-G) 染色にて塩基性を示す広めの細胞質をもち, 核は類円形で偏在傾向がみられ形質細胞への分化がうかがわれるものであった. 大型の芽球や形質細胞, 類上皮細胞も散見された. 他の1例では, 腫瘍細胞は主として中型で広めの細胞質を有し, 類円形の核には偏在傾向がみられた. M-G染色にて塩基性を示し, 核周明庭も認められた. また形質細胞へ分化を示す芽球や, 中等数の類上皮細胞も混在していた. 細胞標本ではlymphoepitheliallesionは認められなかった.低悪性度MALTリンパ腫を細胞標本のみから診断することはときとして困難であるが, 発生部位や, 特徴的な細胞所見を考慮すれば診断可能であると考えられる.