Plasmacytoid Dendritic Cells Producing Interferon-α (IFN-α) and Inducing Mx1 Play an Important Role for CD4(+) Cells and CD8(+) Cells in Necrotizing Lymphadenitis.

We confirmed the characteristic clinical features of necrotizing lymphadenitis (NEL) in 66 cases (23 male, 43 female) in Japan, which included high fever (38-40°), painful cervical lymphadenopathy (62/66, 93.9%), and leukopenia (under 4,000/mm(3)) (25/53, 47.2%), without seasonal occurrence, in a clinicopathological, immunohistochemical, electron microscopic serological study. Patient age varied from 3-55 years, and 72.7% (44/66) of patients were younger than 30 years. Histopathology of NEL was characterized by the presence of CD8(+) immunoblasts, CD123(+) cells (plasmacytoid dendritic cells; PDCs), histiocytes and macrophages phagocytizing CD4(+) apoptotic lymphocytes, but no granulocytes or bacteria. The number of PDCs and CD8(+) cells in lesions tended to increase with time, and PDCs tended to be larger and irregular in the lesions compared with the non-lesion tissue of the lymph nodes. In addition, PDCs showed no temporal morphological change in the lymph nodes. The number of CD4(+) cells in the lymph node lesions sharply decreased from the 2nd to the 4th week, and then tended to increase; however, CD4(+) cells gradually decreased with time in non-lesion tissue. PDCs may produce interferon-α (IFN-α), which induces Mx1 expression. Strong Mx1 immunoreactivity is indicative of IFN-α production. IFN-α induces transformation of CD8(+) cells into immunoblasts, as well as phagocytosis of apoptotic cells derived from CD4(+) cells by macrophages. Thus, PDCs may play an important role with immune cells, including CD8(+) and CD4(+) cells, in necrotizing lymphadenitis.

Necrotizing lymphadenitis (NEL) is a systemic disease characterized by blastic transformation of CD8+ cells and apoptosis of CD4+ cells.

This clinicopathological, immunohistochemical, electron microscopic, and serological study of 382 cases (148 male, 234 female) of necrotizing lymphadenitis (NEL) in Japan confirms NEL as a self-limited disease with characteristic clinical features: high fever (38-40 °C), painful cervical lymphadenopathy (88.3 %), and leukopenia (under 4,000/mm(3)) without seasonal occurrence. Patient age varied from 5 to 80 years, but 62.8 % was younger than 30 years. There were five recurrent cases and four familial cases. In several cases, elevated serum aminotransaminase and antinuclear antibodies were found. Early in the disease, peripheral blood CD8+ cells were more abundant than CD4+ cells, but CD8+ cells decreased gradually with clinical progression, leading to an increasing ratio of CD4+/CD8+ cells during clinical course. Morphological features of involved lymph nodes are numerous CD8+ large immunoblasts, smaller CD4+ lymphocytes, plasmacytoid dendritic cells, histiocytes, and macrophages, the latter with phagocytized CD4+ apoptotic lymphocytes. Granulocytes are generally absent. These characteristics suggest that NEL is a reactive disease characterized by diploid disrupted CD4+ cells and CD8+ cells transforming to blastic cells. The etiology of the disease remains unknown, although viral infection is suggested, and its pathogenesis might include autoimmunity. Clinical characteristics and cytological and histological findings on lymph node biopsies can improve NEL diagnosis.

Primary gastric synovial sarcoma: molecular diagnosis and prediction of prognosis.

A 42-year-old Japanese woman complained of upper abdominal pain. Endoscopic examination demonstrated an elevated lesion in the body of the stomach, and a biopsy specimen demonstrated proliferation of atypical spindle cells. She underwent partial gastrectomy; the resected tumor measured 3.5 × 2.8 × 1.2 cm in size. Histological examination disclosed the haphazard proliferation of spindle cells in the mucosa mixed with less prominent epithelioglandular component. The spindle cells were positive for cytokeratin, vimentin, EMA and CD99, but not for KIT, DOG1, desmin or S100. Reverse transcription-polymerase chain reaction using paraffin sections amplified a SYT-SSX1 chimera transcript. A diagnosis of synovial sarcoma was made. There has been no sign of recurrence or metastasis for 6 years after the operation. Synovial sarcoma in the stomach is very rare. Since differential diagnosis of synovial sarcoma from carcinosarcoma and mesenchymal tumors is critical for the treatment and prediction of prognosis, accurate diagnosis with molecular analysis is essential.

Temporal differences of onset between primary skin lesions and regional lymph node lesions for tularemia in Japan: a clinicopathologic and immunohistochemical study of 19 skin cases and 54 lymph node cases.

For tularemia, a zoonosis caused by the gram-negative coccobacillus Francisella tularensis, research of the relation between skin lesions and lymph node lesions has not been reported in the literature. This report describes skin lesions and lymph node lesions and their mutual relation over time for tularemia in Japan. Around the second day after infection (DAI), a subcutaneous abscess was observed (abscess form). Hand and finger skin ulcers formed during the second to the fourth week. Subcutaneous and dermal granulomas were observed with adjacent monocytoid B lymphocytes (MBLs) (abscess-granulomatous form). From the sixth week, large granulomas with central homogeneous lesions emerged diffusely (granulomatous form). On 2-14 DAI, F. tularensis antigen in skin lesions was detected in abscesses. During 7-12 DAI, abscesses with adjacent MBLs appeared without epithelioid granuloma (abscess form) in regional lymph nodes. During the second to fifth week, granulomas appeared with necrosis (abscess-granulomatous form). After the sixth week, large granulomas with a central homogeneous lesion (granulomatous form) appeared. F. tularensis antigen in lymph node lesions was observed in the abscess on 7-92 DAI. Apparently, F. tularensis penetrates the finger skin immediately after contact with infected hares. Subsequently, the primary lesion gradually transfers from skin to regional lymph nodes. The regional lymph node lesions induced by skin lesion are designated as dermatopathic lymphadenopathy. This study revealed temporal differences of onset among the skin and lymph node lesions.

lmmunoelectron microscopic examination of cord blood CD5+ B cells.

In this study, we have categorized cord blood CD5(+) B cells, which were examined using the horseradish peroxidase-colloidal gold double labeling immunoelectron microscopy, into three subtypes based on their morphology and immunohistochemical characteristics. Type 1a cells and type 1b cells (9% and 17% of the CD5(+) B cells, respectively) had few cytoplasmic organelles, a high nuclear/cytoplasmic (N/C) ratio (0.66 +/- 0.03 and 0.58 +/- 0.04, respectively), and a low nuclear contour index (NCI) value (1.56 +/- 0.30 and 1.50 +/- 0.27, respectively), whereas type 2 cells (74% of the CD5(+) B cells) had a low N/C ratio (0.44 +/- 0.11) and a high NCI value (2.05 +/- 0.68). Type 2 cells, which had many cytoplasmic organelles, frequently had several uropod-like processes that bound to the gold particles. The N/C ratios clearly showed that there were significant differences among the three types of CD5(+) B cells (p < 0.01), and between CD5(+) T cells and the three types of CD5(+) B cells (p < 0.05). For the NCI values, only type 1b and type 2 cells showed a significant difference (p < 0.05). These findings suggest that type 1a cells are transformed into type 1b cells, and then into type 2 cells.