Takashi Joshita

Reactive follicular hyperplasia in the lymph node lesions from systemic lupus erythematosus patients: A clinicopathological and immunohistological study of 21 cases

To clarify the clinicopathological and immunohistological findings of reactive follicular hyperplasia in systemic lupus erythematosus (SLE) lymphadenopathy, we examined 21 such cases, including four males and 17 females. Three main patterns could be delineated: pattern A, histological features of Castleman’s disease (n= 6); pattern B, follicular hyperplasia with pronounced arborizing vasculature in the paracortex resembling T‐zone dysplasia with hyperplastic follicles (n= 6); and pattern C, follicular hyperplasia without any other specific findings (n= 9). The patients who showed patterns A and B on histology were all female with a median age of 36 years, and presented with the lymphadenopathy within 4 months, some before a definitive diagnosis could be made. The group with pattern C included four males and five females with an age ranging from 20 to 58 years (mean, 37 years). In seven of them, the lymphadenopathy was noted 6 months or more after the therapy had been initiated. In a virological study, a small to moderate number of the lymphoid cells were positive for the Epstein–Barr virus‐encoded small RNA in five of 10 cases examined. Human herpesvius 8 was not detected in the four cases examined by polymerase chain reaction and immunohistochemistry. The present study demonstrated that SLE lymphadenopathy showed histological variety and occasionally represented histopathological findings of multicentric Castleman’s disease or findings similar to T‐zone dysplasia with hyperplastic follicles in the biopsied specimens. We emphasize that careful attention to these morphological features, together with clinical and laboratory examinations, should allow a firm diagnosis of SLE to be made, providing information that is pertinent to the treatment of the disease. Moreover, disarray of the follicular dendritic cell (FDC) network, which could be easily detected by immunohistochemistry, was found in approximately 60% of our series. SLE lymphadenopathy should be listed as one of the diseases occasionally associated with disarray of the FDC network, although its clinicopathological significance remains unclear.

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.

Diagnosis of cardiac thrombosis in patients with atrial fibrillation in the absence of macroscopically visible thrombi

Cardiac thrombosis due to atrial fibrillation (AF) has been recognized as the most common cause of cerebral embolism. However, sometimes no macroscopic thrombus is found at autopsy in the heart of a victim of this type of cerebral embolism. We investigated morphological changes in the left atrial endocardium of 31 patients (including 21 cases with AF) who had died of cerebral embolism. “Rough endocardium” (RE) seen macroscopically provided evidence for the existence of atrial thrombosis. The RE that appeared in AF cases was due to a granular and wrinkled appearance of the endocardium associated with oedematous and fibrous thickening. Fibrin-thread deposits were also always distinguishable. Mural thrombi and oedema with neutrophil infiltration in the subendocardium could be seen under the microscope. Small areas of endothelial denudation and thrombotic aggregations were commonly observed by scanning electron microscopy (SEM). These SEM lesions were significantly more frequent in cases with AF than in controls (P< 0.001). The diagnostic success rate for atrial thrombosis among cases with AF increased from 33.3% to 81% when thrombi proven by histological investigation of the areas with RE were added. Left atrial RE may be an anatomically relevant finding for the existence of atrial thrombosis with AF, when the thrombosis cannot be detected upon gross observation at autopsy.

Topographical study on arteriosclerotic lesions at the bifurcations of human cerebral arteries

SummaryWe have studied the topographical distribution of arteriosclerotic lesions at the bifurcation of the internal carotid-anterior cerebral-middle cerebral arteries (internal carotid bifurcation) and of the middle cerebral artery-first temporal branch (first bifurcation of M.C.A.) in humans. The arteriosclerotic lesions showed a distinct pattern with a high incidence on the outer walls of the daughter vessels and at the inner curvatures in the bifurcations where wall shear stress was believed to be relatively low. However, there were differences in the distribution of the lesions between the internal carotid bifurcations and the first bifurcations of M.C.A.. The former are considered to be three-dimensionally unsymmetrical and curved, and the latter symmetrical and straight. The present study suggests that lower shear stress is of considerable importance in both the initiation and localization of arteriosclerotic lesions, and that study of the three-dimensional blood vessel architecture and blood flow patterns needs to be done to clarify the role of hemodynamic forces in atherogenesis.

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.

Three-dimensional analysis of human carotid atherosclerotic ulcer associated with recent thrombotic occlusion.

To clarify the mechanism of ulcer formation of atherosclerotic plaques in human carotid arteries, autopsy investigations were performed on eight patients who had died of cerebral infarction due to recent carotid thrombosis. Eleven control patients who had carotid atherosclerosis without thrombosis were also investigated. Histological changes of the arteries in serial sections were reconstructed three‐dimensionally. Each artery with occlusive thrombosis was found to have an intimal ulcer at the head of the thrombus on the proximal slope near the base of the thickened atheromatous plaque at the carotid sinus. Most ulcers formed obliquely or longitudinally, were parallel to the vessel axis, had a fusiform shape, and measured 7± 2× 3 ± 1 mm (mean ± s.d.). The ulcers arose by marginal separation of the innermost layer from the underlying layer of the stratified intima. An underlying atheroma developed along the borders of these intimal layers reaching the subendothelium, with thinning of the intimal cap to less than 150 μn. The process of ulceration may be generated by vessel injury induced by hemodynamic forces, such as tensile forces and shear stress. The ulcer may extend along the fragile region where the wall may exhibit uneven compliance due to differences in the tissue structures of each intimal layer. Futhermore, macrophages may play a key role in ulcer formation.

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.

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.

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.

Encapsulated papillary carcinoma of the thyroid gland: Clincopathological and cytoflurometric study in comparison with non-encapsulated papillary carcinomy

Clinicopatholigical and cytofluroremetric studies were performed on nine encapsulated (EPC) and 23 non‐encapsulated (non‐EPC) carcinomas of the thyroid gland. The average age of the patients with EPC was 33 years, which was significantly younger than that of those with non‐EPC. The average tumor size of EPC was twice as large as that of intraglandular non‐escapsulated carcinoma. All patients with EPC were alive without disease, but three out of 23 patients with non‐EPC had a recurrence of the disease of died. Cytofluorometric studies showed that the mean nuclear DNA content and percentage of tumor cells in the S‐G2M phase of EPC were lower than that of non‐EPC. According to the DNA histogram pattern, all EPC showed distinct modal DNA values in the diploid or near diploid region of normal cells. However non‐EPC, especially extra‐glandular non‐encapsulated papillary carcinoma, showed a wide variety of DNA histogram patterns. The present study suggested that EPC is a distinct subtype of papillary carcinoma of the throid gland clinicopathologically and the cytofluorometrically it is differnt from non‐EPC.