Pulmonary sclerosing hemangioma associated with familial adenomatous polyposis.

A 45-year-old woman presented with asymptomatic solid tumor in the lower right lobe of the lung. Histologically, the tumor comprised a monolayer of surface cells and round stromal cells displaying sclerotic areas. Immunohistochemical studies suggested a diagnosis of sclerosing hemangioma. Interestingly, morular lesions were also observed. Analyses of the gastrointestinal (GI) tract showed mild familial adenomatous polyposis (FAP) and numerous fundal gland polyps, indicating attenuated FAP (AFAP). All components of the sclerosing hemangioma displayed aberrant nuclear and cytoplasmic expression of beta-catenin. However, such findings were much weaker in adenomas of the GI tract and were barely observed in fundal gland polyps. These results strongly suggest an association between sclerosing hemangioma and the AFAP. To the best of our knowledge, this is only the second report of lung tumor associated with FAP and is the first describing an association with sclerosing hemangioma. A new category of FAP-associated lung tumors may be indicated.

Enhancement of IL-7 following irradiation of fetal thymus.

The effect of ionizing radiation on intra-thymic T cell development was investigated using a fetal thymic organ culture (FTOC) method in vitro. When double-negative (DN) fetal (day 15) thymocytes were co-cultured with an irradiated (25 Gy) fetal (day 15) thymus in the absence of direct contact or mitogenic stimulation, the induction of TCRgammadelta+ T cells was observed. About 50% of the TCRgammadelta+ T cells developed after 4-day-co-culture with the irradiated fetal thymus, whereas only a few TCRgammadelta+ T cells developed after co-culture with the non-irradiated fetal thymus. About 50% of the TCRgammadelta+ T cells were CD8+ cells with alphabeta heterodimeric chains. Cultured supernatants of the irradiated fetal thymi also induced the differentiation from DN thymocytes to CD8+ TCRgammadelta+ T cells after 3-day-culture. To clarify the factor in the cultured supernatants, several neutralizing antibodies (Abs) were used. Only anti-IL-7-Ab inhibited the differentiation from DN thymocytes to CD8+ TCRgammadelta+ T cells. RT-PCR revealed the increased expression of IL-7 mRNA in the fetal thymus 24 hours after radiation. Electron microscope studies demonstrated proliferative epithelial cells in the irradiated fetal thymus. These findings strongly suggest that fetal thymic epithelial cells affected by irradiation proliferate and enhance the production of IL-7, which induces the differentiation of CD8+ TCRgammadelta+ T cells from DN thymocytes.

Amyloid A gastrointestinal amyloidosis associated with idiopathic retroperitoneal fibrosis. Report of a rare autopsy case and review of the literature.

We report a rare autopsy case of secondary gastrointestinal amyloid A (AA) amyloidosis associated with idiopathic retroperitoneal fibrosis (IRF) in a 67-year-old woman. Masses were identified around the aorta and inferior vena cava in her abdomen. Histologically, plasma cell infiltration was observed within fibrotic areas. Because no specific cause for the inflammatory mass was apparent, we diagnosed it as IRF. Steroid therapy, which usually reduces IRF masses, proved ineffective, and malabsorption syndrome developed 4 years later. On autopsy, amyloid protein was present systemically in the vascular walls of several organs, and deposition was highest in the gastrointestinal mucosa. Amyloid protein was identified as AA type, strongly suggesting that the amyloidosis was secondarily induced by IRF. To our knowledge, only 2 other cases of IRF-associated amyloidosis have been reported. Two of the 3 patients of these cases were women who showed resistance to steroid therapy.

Immature dendritic cells (CD11c+ CD3- B220- cells) present in mouse peripheral blood.

It is well known that dendritic cells (DCs) are developed from the peripheral blood of mice when peripheral blood mononuclear cells (PBMCs) are cultured with GM-CSF. We have previously found that immature DCs are present in the blood even in humans. In the present study, we show that CD11c+ CD3- B220- cells in the mouse peripheral blood are immature DCs. The percentage of CD11c+ CD3- B220- cells in the (PBMCs) of normal mice ranges from 0.5 to 2.5%. The CD11c+ CD3- B220- cells in the PBMCs show dendrites, similar in shape to the CD11c+ CD3- B220- cells in the spleen, which are thought to be DCs definitely. However, they have practically no capacity to stimulate the proliferation of allogeneic T cells, and show a lower expression of MHC class II, B7-1 and B7-2 than CD11c+ CD3- B220- cells in the spleen. When the CD11c+ CD3- B220- cells in the PBMCs are cultured with GM-CSF, they show not only the potent ability to stimulate the proliferation of allogeneic T cells but also a higher expression of MHC class II, B7-1 and B7-2. Moreover, they migrate into the spleen when they are injected intravenously. These results suggest that CD11c+ CD3- B220- cells in the PBMCs are immature DCs, and that they migrate into the spleen, where they mature.

Ectopic pituitary adenoma with malignant transformation.

We report here a case of ectopic pituitary adenoma with malignant transformation after repeated relapses. First, an ectopic pituitary adenoma producing follicle-stimulating hormone was found in the nasal cavity extending to the frontal cranial fossa. Despite repeated surgical resections of the tumor, it recurred three times in 2 years. The tumor gradually showed cellular atypia, mitosis, and necrosis. Immunohistochemical analyses revealed that the expressions of proliferating cell nuclear antigen and MIB-1 increased progressively. Moreover, the expression of p53 was detected at the second recurrence. Finally, at the third recurrence the tumor showed dissemination to the subarachnoid space and multiple metastases in the brain. The patient died of the tumor 10 months after the last resection. These findings indicate that the ectopic pituitary adenoma became malignant. To our knowledge, this is the first report on malignant transformation of ectopic pituitary adenoma. It is important to know that ectopic pituitary adenomas show malignant transformation and that the above parameters (proliferating cell nuclear antigen, MIB-1, and p53) may be useful indicators of the malignant potential of both ectopic and sellar pituitary tumors.

Kimura's disease with unusual eosinophilic epithelioid granulomatous reaction: a finding possibly related to eosinophil apoptosis.

We report and discuss a case of Kimura's disease with an unusual eosinophilic epithelioid granulomatous reaction. A 3-year-old Japanese boy with eosinophilia and a high concentration of IgE developed lymphadenopathy and multiple cervical masses. A lymph node biopsy demonstrated the infiltration of eosinophils in the stroma, which is consistent with the findings of Kimura's disease. Interestingly, a number of apoptotic eosinophils was detected in the infiltrating eosinophils. Multiple epithelioid granulomas with central eosinophilic abscesses and necrosis were also observed. Macrophages and giant cells had phagocytosed the apoptotic eosinophils at the edge of the granulomas. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay showed that the TUNEL-positive eosinophils were both in the macrophages and in the central eosinophilic abscesses of the granulomas. These findings suggest that the eosinophils had undergone an accelerated apoptosis in this case of Kimura's disease, and that the epithelioid granulomas were produced by phagocytosis of the apoptotic eosinophils by macrophages.

Marked increase in number of dendritic cells in autoimmune-prone (NZW x BXSB)F1 mice with age.

Here, we report that the number of CD11c(+)CD3(-) B220(-) cells increases in autoimmune-prone male (NZW x BXSB)F1 (W/BF1) mice with age. The CD11c(+)CD3(-)B220(-) cells from W/BF1 mice show a typical stellate shape and induce the proliferation of T cells. In the CD11c(+)CD3(-)B220(-) cells from W/BF1 mice, CD11b (Mac-1alpha), NK 1.1, and CD95 (Fas) are upregulated in comparison with normal mice, while the expression of CD8alpha, CD117 (c-kit), CD135 (Flk-2/Flt-3), and Sca-1 decreases. There is a significant increase in Flt-3L (FL) mRNA in the bone marrow of W/BF1 mice with age. Moreover, activated hemopoietic cells express high levels of FL. The injection of CD11c(+)CD3(-)B220(-) cells from old W/BF1 mice to young W/BF1 mice transiently induces autoimmune disease (thrombocytopenia). These results suggest that hyperproduction of FL from activated hemopoietic cells induces a dramatic increase in the number of dendritic cells in aged W/BF1 mice, followed by the acceleration of autoimmunity.

Radiosensitive hemangiopericytoma in the soft palate.

Hemangiopericytomas are uncommon neoplasms of vascular origin, and rarely arise in the pharynx. We report a case of a 78-year-old female with hemangiopericytoma in her soft palate exhibiting prominent radiosensitivity. Hemangiopericytomas are considered to be radioresistant and wide local excision is a treatment of choice, but their nature is widely variable. In treating aggressive hemangiopericytomas, radiation therapy can be selected.