Resolution of immune thrombocytopenic purpura associated with extranodal B-cell lymphoma of the petroclival region after radiotherapy.

BACKGROUND: Secondary immune thrombocytopenic purpura (ITP) associated with extranodal B-cell non-Hodgkin's lymphoma (NHL) is extremely rare. The optimal management is not established. We report a first case of ITP in association with extranodal B-cell NHL originating in the lower petroclival region, successfully managed by local tumor control using conventional radiotherapy. CASE DESCRIPTION: A 75-year-old man presented with a two-month history of hearing loss, hoarseness, and dysphagia. Neuroimaging revealed a large enhanced lesion in the left lower petroclival bone near the jugular foramen. Isolated unilateral parotid lymphadenopathy was also noted. Preoperative laboratory findings were normal, except for elevation of serum soluble interleukin-2 receptor level. A suboccipital craniotomy was performed and a biopsy sample was taken. Histological and immunohistochemical examination confirmed small B-cell lymphoma with plasmacytic differentiation. After initiation of radiotherapy, thrombocytopenia (24,000/µl) rapidly developed. Serological and bone marrow examination confirmed ITP. Prednisone was given at 1 mg/kg/day and radiation therapy was continued. After more than 32Gy, platelet count rapidly normalized. Radiotherapy to the tumor site achieved local tumor control and ITP was resolved. No evidence of recurrence and normal platelet count were confirmed at the two-year follow-up examination. CONCLUSION: Local control of the tumor was considered important in the resolution of secondary ITP in association with extranodal NHL of the skull base region.

[A Case of gastric endocrine cell carcinoma successfully treated by FU plus irinotecan(CPT-11)adjuvant therapy against recurrent metastases].

A case of gastric endocrine cell carcinoma successfully treated by FU (5-FU/UFT) +irinotecan (CPT-11) adjuvant therapy against recurrent metastases is reported with some discussion. A 69-year-old man was admitted to our hospital with severe anemia. He was diagnosed with advanced gastric cancer, T3N1H0P0M0, Stage IIIa. Total gastrectomy with pancreato-splenectomy with D2 lymph node dissection was done for curative resection. The pathological diagnosis was gastric endocrine cell carcinoma because Grimelius and Chromogranin A stained positive histologically. Seven months after operation, recurrent liver metastases with tumor embolism of the portal vein were revealed by enhanced CT examination. FU (5-FU/UFT) +CPT-11 was done as the first-line adjuvant chemotherapy. Metastatic lesion of the liver and portal vein tumor embolism was decreased. Tumor marker CA19-9 level was also decreased and within normal limits. This therapy was evaluated as a partial response (PR) in twelve months and the patient died three years and eight months after operation. Gastric endocrine cell carcinoma is known as a potentially highly malignant tumor. But in our case FU+CPT-11 controlled growth of the recurrent tumor. Based on this finding, we recommend adjuvant chemotherapy by FU+CPT-11 for gastric endocrine cell carcinoma.

B-cell lymphoma associated with Sjögren's syndrome among Japanese patients: a clinicopathologic and immunohistochemical study of 15 cases.

To clarify the clinicopathological findings of B-cell lymphoma associated with Sjögren's syndrome (SJS) among Japanese Patients, 15 individuals with this disease were studied. The patients, 14 females and one male, ranged in age from 41 to 73 years with a median age of 56 years. These lymphomas arose not only in the salivary gland (n=4) but also in other mucosal extranodal sites (n=5). Histologically, six cases were marginal zone B-cell lymphoma (MZBL) of the mucosa-associated lymphoid tissue (MALT) type, three cases were diffuse large B-cell lymphoma (DLBCL) + MALT type lymphoma, two cases were nodal MZBL and one case each was small lymphocytic lymphoma, Burkitt's lymphoma, CD10(+) DLBCL and DLBCL + nodal MZBL. Using in situ hybridization, numerous Epstein-Barr virus(+) tumor cells were detected only in the case of Burkitt lymphoma. There were no human-herpes type 8(+) tumor cells in any of the 15 cases. There was no API2-MALT1 fusion transcript in any of the eight cases examined. B-cell lymphoma associated with SJS also frequently affected extranodal organs in patients from Japan as well as from patients in Western countries. The majority of B-cell lymphomas in patients with SJS also appear to be low-grade MZBLs or high-grade lymphomas probably derived from MZBL both in Western countries and in Japan.

Gastric yolk sac tumor complicated with beta-human chorionic gonadotropin-producing metastases.

This report describes the case of 74-year-old man who had a gastric yolk sac tumor complicated with beta human chorionic gonadotropin (beta hCG) producing metastases. He was a heavy drinker. He was admitted to the hospital for abdominal pain and fullness. Based on computed tomography and gastric endoscopy he was diagnosed to have gastric cancer that had metastasized to the liver, lung and lymph nodes. The level of serum alpha fetoprotein (AFP) was high at 523 ng/mL. He died of multiorgan failure six days after admission. The autopsy revealed the stomach tumor to be an AFP-positive yolk sac tumor. Lymph node metastases showed the same characteristics as the stomach tumor. However, the lesions on the liver and lung were negative for AFP and positive for hCG. The yolk sac tumor seemed to have retrodifferentiated to form an hCG-producing tumor in the metastatic lesions. A gastric yolk sac tumor is extremely rare and only eight cases of gastric yolk sac tumors have been previously reported in the literature. To avoid a misdiagnosis, careful attention should be paid to the above-mentioned morphological features and immunohistochemical findings, in addition to the clinical findings.

Systemic sclerosis after interferon alphacon-1 therapy for hepatitis C.

A 66-year-old woman developed systemic sclerosis (SSc) after receiving interferon alphacon-1 (IFNalphacon-1; consensus interferon) therapy for chronic hepatitis C. She suffered from Raynauds phenomenon about 1 year after a course of IFNalphacon-1 therapy. The combination of proximal scleroderma, Raynauds phenomenon, and ANA positivity led to a diagnosis of systemic sclerosis (SSc). IFN has multiple effects on the immune system and is known to trigger the development of autoantibodies, as well as the onset or exacerbation of autoimmune disease. We suspect that the immunomodulatory effects of IFNalphacon-1 triggered the clinical manifestations of SSc in this patient. To our knowledge this is only the third case of SSc after IFNalpha therapy, and it is the first case associated with IFNalphacon-1 therapy.

Distribution of Epstein-Barr virus in systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis) with associated lymphadenopathy: a study of 49 cases.

Among systemic rheumatic diseases (SRDs), lymphadenopathy is frequently found in patients with rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) may occur in patients following methotrexate therapy for RA and dermatomyositis (DM). However, little is known about the distribution of EBV in reactive LPDs in patients with SRDs who had no history of methotrexate therapy. We analyzed 49 such patients (SLE=25, RA=23, DM=1) for the presence and distribution of EBV+ cells using Epstein-Barr virus (EBV)-encoded small RNA (EBER) specific in situ hybridization. A positive signal for EBERs was identified in 9 (SLE=5, RA=4) (18%) of 49 cases, and 3 main distribution patterns of EBER+cells could be delineated: pattern A, more than 500 EBER-positive cells were located in the germinal centers as well as interfollicular area (SLE=2); pattern B, EBER + cells were located in a few germinal centers (RA=2); and pattern C, up to 100 EBER+ cells were located in the interfollicular area (SLE=3, RA=2). Recent EBV infection may be a cause of lymph node lesion in only 2 cases of patients with pattern A. However, the pathognomonic significance of pattern B and pattern C EBER + cell distribution patterns still remains unclear. Our study indicates that the underlying immune deficits of patients with SRDs may also play an important role in the development of EBV-associated LPDs in SRDs, as previously suggested by several authors.

Clinical implication of florid reactive follicular hyperplasia in Japanese patients 60 years or older: a study of 46 cases.

Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in middle-aged or elderly patients requiring biopsy is a relatively uncommon phenomenon as compared with that in younger age groups. Between 1984 and January 2004, we encountered 46 patients, aged 60 years or older, in whom histology of biopsied lymph node specimens showed inappropriate FRFH for the patient's age. An apparent cause of lymphadenopathy was initially identified in 17 cases (37%): 11 with autoimmune disease and related disorders, 3 with cancer-reactive lymphadenopathy, 2 with Epstein-Barr virus-associated lymph node lesion exhibiting transient autoimmune-disease-like clinical findings, and 1 with atypical mycobacterial infection. Among 29 patients without specific etiology, 16 patients (55%) exhibited histologic findings of progressive transformed germinal center (PTGC). Only 1 of our patients developed malignant lymphoma during the follow-up period. The present study indicates that PTGC is included in the etiology of FRFH in elderly Japanese patients as well as imbalance of the immune system such as autoimmune-disease-associated lymphadenopathy and idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia. By in situ hybridization, Epstein-Barr virus genomes were demonstrated in only 6 (15%) of 39 cases examined.

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 Hodgkin's 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.

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 Sjögren's 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.