Satoshi Ban

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.

Progressive Transformation of Germinal Centers: A Clinicopathological Study of 42 Japanese Patients:

To clarify the clinicopathological features of progressive transformation of germinal center (PTGC) unrelated to nodular lymphocyte predominant Hodgkins lymphoma in Japanese patients, we reviewed 42 cases and compared the results with those of the United States and Germany. Our results were similar to theirs, with male predominance (M/F ratio, 3:1) and the presentation of a solitary asymptomatic enlarged lymph node in the head and neck area as the common features. However, in Japan, PTGC occurs more frequently in elderly patients. In this study, 12 (29%) of the patients with PTGC were aged 60 years or more. Thirteen patients (31%) with lymphadenopathy in the neck and head area had developed localized chronic inflammation (chronic sialoadenitis=4, chronic tonsillitis=3, infectious epidermal cyst=2) or an autoimmune disorder (hyperthyroidism=2 and bronchial asthma=2). None of the patients developed a malignant lymphoma during the follow-up period of 5 to 238 months (median 27 months). Histologically, in a single longitudinal section of the lymph node, the PTGC occupied up to 5% of the total follicles in 22 patients, 5-10% in 10, 10-20% in 7, and more than 20% in 3. In 5 (12%) patients, an association with prominent marginal zone hyperplasia was also noted. This study also indicates that nodal involvement by various low-grade B-cell lymphomas exhibiting marginal zone distribution patterns should be considered as a differential diagnosis of PTGC. Moreover, in Japan, PTGC is thought to be involved in the etiology of florid reactive follicular hyperplasia in elderly patients.

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.

Primary pulmonary low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with prominent hyalinosis. A case report.

We report a case of primary pulmonary low-grade marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type with prominent sclerosis, which morphologically resembled pulmonary hyalinizing granuloma (PHG) or inflammatory pseudotumor (IPT) of the lung. The patient, a 66-year-old Japanese female with a history of Sjögrens syndrome and primary biliary cirrhosis, presented with a lower left lobe mass 6.8 cm in diameter. Histologically, the lesion is characterized by dense bundles of collagen with scattered plasma cells, mature small lymphocytes, and histiocytes among the collagen bundles. Only the peripheral area of the nodule contained dense lymphoplasmacytoid and histiocytoid infiltrates. A few centrocyte-like cells were obscured by the numerous plasma cells and plasmacytoid cells. In addition, lymphoepithelial lesions and colonalized lymphoid follicles were identified by immunohistochemistry alone. Although PHG and IPT are unlikely to be confused with pulmonary MALT-type lymphomas, the present case suggests that MALT-type lymphoma should be added to the list of differential diagnoses for PHG and IPT.

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.

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.

A case of primary leptomeningeal malignant melanoma diagnosed by cerebrospinal fluid cytology.

背景:髄液細胞診で診断し得た脳軟膜原発悪性黒色腫の1例を報告する.症例:20歳, 男性. 1997年7月頃より肩こり, 頭重感出現.1998年1月頃よりそれら症状が増悪, 時に嘔吐, 嘔気があり他院にて頭部MRLCT検査など施行したが異常はみつからなかった. その後症状が悪化したため当院に精査加療目的にて入院となった. 初回の髄液細胞診検査ではN/Cが高く, 核小体の腫大した異型細胞が孤立散在性に認められ, melanin顆粒を含む細胞は気付かれなかった. 悪性リンパ腫の疑いにて免疫細胞化学的検索を施行したが, 確定診断には至らなかった.髄液細胞診の再検査では孤立散在性の異型細胞に加え, シート状のゆるい結合をもつ細胞集塊が認められた. 細胞質内に茶褐色穎粒を有する異型細胞も認められ, melanin産生性の腫瘍が疑われた. それらの細胞はDopa反応, Fontana-Masson染色に陽性を示し, 免疫細胞化学的検査ではS-100蛋白, HMB-45に強陽性を示したことより悪性黒色腫と診断された.結論:悪性黒色腫の診断はいずれの部位においても, melanin色素に気付くかどうかが正確な診断の入り口であるが, 髄液細胞診では検体量が一般に少量で, 出現細胞が少ないことが多いので, ことのほか注意深い観察を行うことが必要である. また, melanin穎粒であるか否かを細胞化学的あるいは免疫細胞化学的に証明することも重要である.