Shunichi Shimano

Clinical Implication of Idiopathic Plasmacytic Lymphadenopathy with Polyclonal Hypergammaglobulinemia: A Report of 16 Cases

Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia is considered identical to multicentric Castlemans disease (MCD) reported in western countries. Clinically, both IPL and MCD are characterized by multicentric lymphadenopathy, prominent polyclonal hypergammaglobulinemia, elevated erythrocyte sedimentation rate, elevated serum interleukin-6 concentration, bone marrow plasmacytosis, and various abnormal laboratory data such as anemia and positive autoantibodies. However, IPL has a significantly better 5-year survival rate than that of MCD. Moreover, none of the present 16 cases developed Kaposis sarcoma or B-cell lymphoma. Histologically, the interfollicular area contains a sheet of polytypic mature plasma cells in both IPL and MCD. In MCD, the majority of lymphoid follicles had hyaline-vascular germinal centers. However, lymphoid follicles of IPL usually exhibit a hyperplastic germinal center. Immunostaining also demonstrated a normal/ reactive follicular dendritic cell network pattern in the germinal center of IPL. Moreover, there were no human herpes virus-8-positive cells detected by immunohistochemistry. The overall clinicopathologic and immunohistochemical findings of our 16 cases suggest that IPL is distinct from MCD reported in Western countries.

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.

Proliferative kinetics of the leukemic cells in meningeal leukemia.

The proliferative kinetics of leukemic cells was investigated in the cerebrospinal fluid (CSF) and the leptomeninges of 5 patients with meningeal leukemia (ML) and 15 selected autopsies showing meningeal involvement. The 3H‐thymidine labeling index (TLI), mitotic index (MI) and 3H‐uridine labeling index (ULI) of leukemic cells in the CSF at the time of diagnosis were 0.7 ± 0.2, less than 0.01 and 96.2 ± 0.7%, respectively. The TLI was found to be higher at the time of recurrence than at the initial diagnosis of meningeal leukemia. The grade of leukemic cell infiltration was classified according to Prices criteria. The mitotic index was also estimated on the histologic sections. An infiltration of Grade 2 or greater was observed in all 4 patients who had not received an intrathecal administration of methotrexate (MTX). The clinical course of 2 patients with a higher MI (0.88 and 0.32%) was shorter than the other 2 (0.03 and 0.01%). In the patients who did not show clinical manifestations of ML, the infiltration of leukemic cells in the leptomeninges was mild in degree, and the MI was less than 0.01%. Likewise, mild infiltration and low MI was observed in 8 cases treated with an intrathecal administration of methotrexate. These findings seem to support the general concept that the proliferation of leukemia cells infiltrating leptomeninges is remarkably slow at an incipient stage of ML; then it undergoes a gradual acceleration, possibly slowing down again at an advanced stage of the disease.

Primary marginal zone B-cell lymphoma of the lymph node resembling plasmacytoma arising from a plasma cell variant of Castleman's disease. A clinicopathological and immunohistochemical study of seven patients

Nodal marginal zone B‐cell lymphomas (NMZBL) occasionally represent prominent plasma cell differentiation. Recently, we presented a patient with NMZBL who exhibited histological features that resembled plasmacytoma arising from a localized plasma cell variant of Castlemans disease. To further clarify the clinicopathological, immunohistochemical, and genotypical findings, we studied seven such patients. Clinically, these patients were characterized by localized disease and an indolent clinical course with a slowly growing bulky mass in the affected lymph node. Only one patient exhibited paraproteinemia. Histologically, the lesions were characterized by numerous evenly distrubuted germinal centers in extensive sheets of plasma cells. Various numbers of centrocyte‐like (CCL) cells arranged in a marginal zone distribution pattern occupied the peripheral region of the lymph node. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry showed that all of the lesions contained a monoclonal plasma cell population. In three tumors, a number of the CCL cells had a similar light chain restriction pattern to that observed in plasma cells. Two of the four patients evaluated exhibited clonal bands for the IgH gene by polymerase chain reaction assay. Moreover, the presence of surface IgM+, IgD− and CD27+ CCL− cells suggests that these tumors are derived from memory B‐lymphocytes.

A staging system for multiple myeloma based on the morphology of myeloma cells

Abstract: The morphology of myeloma cells is reported to be one of the prognostic factors in multiple myeloma (MM) patients. We analyzed the prognostic factors, including morphological classification, in 292 patients with MM in order to select poor‐risk patients who should be considered candidates for early intensive chemotherapy, including stem cell transplantation. Multivariate analysis was applied to 90 patients diagnosed between 1989 and 1996, because serum beta‐2‐microglobulin (β2M) has been measured regularly since 1989, and showed that serum albumin, serum β2M, and the morphology of myeloma cells predicted survival. According to these factors, patients were divided into 3 risk groups; a high‐risk group (14%), a intermediate‐risk group (46%) and a low‐risk group (40%). There were significant differences between survival times in these 3 groups (median survival: high‐risk, 16; intermediate‐risk, 22; and low‐risk, 44 months).

Clinical Implication of Dermatopathic Lymphadenopathy Among Japanese: A Report of 19 Cases

To clarify the clinicopathologic and immunohistochemical features of dermatopathic lymphadenopathy not associated with mycosis fungoides among Japanese, 19 patients were studied. Seventy-four percent of the patients were more than 50 years old (median; 63 years, mean 61 years). Systemic symptoms such as fever were recorded in 68% and multicentric lymphadenopathy was noted in 83% of patients. An association of autoimmune disease or positivity of autoantibodies was recorded in 6 patients. Five patients showed cutaneous hypersensitivity reactions to a drug. Histologically, in addition to the dermatopathic lymphadenopathy, numerous immunoblasts were observed in 2 cases and sheet-like proliferation of mature plasma cells in 3 cases. Various atypical or malignant lymphoproliferative disorders exhibiting immunologic abnormalities such as angioimmunoblastic T-cell lymphoma or autoimmune disease-associated lymphadenopathy frequently occur in middle-aged and elderly patients. At least some of the patients with dermatopathic lymphadenopathy should be clinicopathologically differentiated from these lymphoproliferative disorders.

Rectal cancer associated with chronic lymphocytic leukemia

It has been reported that chronic lymphocytic leukemia (CLL) often occurs concomitantly with other malignant neoplasms. However, because CLL is rare in Japan, there are only a limited number of reports of the occurrence of malignant neoplasia in Japanese patients with CLL. We report here the simultaneous occurrence of rectal cancer and CLL in a 57-year-old man. Because the clinical stage of CLL was Rai system I, we decided, in accordance with the National Cancer Institute–Sponsored Working Group guidelines, to monitor him without therapy for CLL until evidence of disease progression, and we performed abdominoperineal resection of the rectum for the cancer. The small rectal tumor was associated with aggressive lymphangiosis carcinomatosa, and multiple nodal metastases were observed in the pool of CLL cells. He died of rectal cancer 7 months after the operation, and autopsy revealed extensive metastases of the cancer. Cellular and humoral immunity is often impaired in patients with CLL, and the defective immunity in this patient may have had an etiological role in the development and rapid progression of the cancer. In the follow-up of CLL patients, we must always be aware of the possible existence of a second malignant disease. Particular attention should be paid to those with defective immunity, and screening should be performed, especially for pulmonary and gastrointestinal malignancies.

Molecular detection of tumor cells at diagnosis invading the bone marrow and peripheral blood of patients with aggressive or indolent lymphomas

We studied tumor cell invasions of bone marrow and peripheral blood in patients with various types of advanced non-Hodgkins lymphoma by amplifying complementarity determining region III using the polymerase chain reaction (PCR) method and developing patient-specific probes. After molecular engineering, we could detect tumor cells in bone marrow from seven of 11 cases and in peripheral blood from six of 11 cases, despite negative results in four cases studied morphologically. Indolent cases were more likely to yield positive results than aggressive cases. The reason may be different biological behaviors among the histological types.

Unilateral Leg Swelling: Differential Diagnostic Issue Other than Deep Vein Thrombosis

It is important to discriminate between deep vein thrombosis (DVT) and conditions that mimic it. Here we report on three patients, who had unilateral leg swelling mimicking DVT. The following diagnoses were found: cellulitis and metastatic abscesses by Staphylococcus aureus bacteremia, inter‐muscular hematoma through femoral muscle injury, venous insufficiency caused by ureteral cancer. The cases of these various disease states serve to remind us that physicians should pay careful attention to unilateral leg swelling, when DVT has been excluded.