Isao Irei

Malignant peripheral nerve sheath tumor arising in benign ancient schwannoma: A case report with an immunohistochemical study

A rare example of malignant transformation in an ancient schwannoma arisng in the right side of the neck of a 51‐year‐old man without any clinical manifestations suggesting neurofibromatosis is described. The tumor, approximately 4 cm at its largest dimension, was well circumscribed and had a direct connection with the sympathetic nerve. Microscopically, the central portion of the tumor showed features of ancient schwannoma characterized by extensive hyalinization with cystic degeneration, scattered spindle cells with hyperchromatic and tapered nuclei, and some symplastic changes. However, predominantly in the outer portion, a proliferation of spindle‐shaped cells with enlarged nuclei was present. The nuclei of these cells showed irregular contours, coarse granular chromatin texture, and conspicuous nucleoli. Mitotic figures and small necrotic foci with scattered apoptotic bodies were also seen. Immunohistochemically, S‐100 protein was almost negative in areas consisting of overtly atypical cells where the mitotic index evaluated with MIB‐1 antibody was 30.5%. In contrast, S‐100‐positive bland spindle cells were scattered in an extensively hyalinized area with a labeling index less than 3%. P53 protein was strongly positive in atypical spindle cells. Although it is a very uncommon event, definite nuclear atypia, frequent mitotic figures, and the existence of small necrotic foci should be recognized as indicating a diagnosis of malignant degeneration of benign schwannoma. Immunohistochemistry would be useful as an ancillary technique in such a setting.

Primary pulmonary primitive neuroectodermal tumor (PNET). A case report.

We describe a rare case of a primary primitive neuroectodermal tumor (PNET) in the lung of a 17-year-old girl. Grossly, the tumor, located in the right lower lobe, was relatively well-circumscribed and whitish to yellowish in color with scattered hemorrhagic necrosis. Microscopically, the tumor was composed of ovoid to polygonal cells with a high nuclear to cytoplasmic ratio and relatively scant cytoplasm, arranged in solid sheets with intervening fine fibrovascular stroma. Immunohistochemically, the tumor was positive for the MIC2 gene product, whereas AE1/AE3, CAM5.2, and a variety of neuroendocrine markers such as chromogranin A, synaptophysin, and ProGRP, were negative. Three months after the lobectomy, recurrent tumors were noted in the mediastinum and right thoracic wall, and she died despite combined chemotherapy and radiation therapy. In this case cytogenetic analysis showed a hypertriploid karyotype with multiple numerical and structural chromosomal aberrations, but failed to disclose distinct evidence of translocation between chromosome 11 and 22. However, the reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated EWS/FLI-1 fusion transcripts, confirming the histopathologic diagnosis of PNET. This case indicates that the primary pulmonary PNET is a highly aggressive neoplasm occurring at a young age, and should prompt combined systemic chemotherapy, even though it is organ-confined.

Cellular Localization of Sphingosine-1-phosphate Receptor 1 Expression in the Human Central Nervous System

Sphingosine-1-phosphate (S1P), a potent lipid mediator, transduces intracellular signals through the activation of S1P receptors (S1PRs). Although S1PRs have been shown to play an important role in the central nervous system (CNS), accurate localization and the function of S1PR1 in the human CNS are still unclear. In this study, we investigated the localization of S1PR1 in the human CNS of postmortem samples, using a rabbit polyclonal antibody, the specificity of which had been well defined. Immunohistochemical investigation of paraffin-embedded sections revealed diffuse granular staining of the gray matter. The signals of the gray matter were much stronger than those of the white matter. The immunohistochemical expression levels correlated well with the results of quantitative real-time RT-PCR-based analysis and Western blotting. Studies using double immunostaining and immunoelectron microscopy revealed that the antigen was strongly expressed in the membrane of the astrocytic foot processes of glia limitans and astrocytes with radial cytoplasm, but not distributed in neurons. In neurological disorders, hypertrophic astrocytes with strong expression of glial fibrillary acidic protein exhibited significantly decreased expression of S1PR1 in contrast to its strong expression in astrocytes forming fibrillary gliosis. These results indicate that S1PR1 is localized in astrocytes, and its expression level may change during the processes that occur after brain damage.

Transformation from follicular lymphoma to high-grade B-cell lymphoma/leukemia with additional t(2;8)(p12;q24), with inverse expressions of c-MYC and BCL-2, and light-chain switch

Transformation from follicular lymphoma (FL) to high‐grade B‐cell lymphoma/leukemia (BLL) has been reported in patients with additional translocations involving the c‐MYC gene. The previously reported cases were related to t(8;14) and t(8;22) but not to t(2;8). Herein is reported an FL that terminated in BLL following additional t(2;8). In accordance with previous reports, increased expression of c‐MYC was observed in the present case but, interestingly, BCL‐2 expression was inversely decreased after the transformation. In addition, the cell‐surface immunoglobulin light‐chain of lymphoma cells was initially κ type and was then gradually replaced with the λ type after transformation. Downregulation of BCL‐2 and light‐chain switch have rarely been reported in previous cases of FL transformation involving c‐MYC, suggesting that additional t(2;8) translocation may play a role in these events.

Sphingosine-1-phosphate receptor 1 is a useful adjunct for distinguishing vascular neoplasms from morphological mimics

Sphingosine-1-phosphate receptor 1 (S1P1) has been shown to play an important role in the migration, proliferation, and survival of endothelial cells. S1P1 of vascular and lymphatic endothelial cells can be detected by immunostaining of paraffin-embedded sections using a rabbit anti-S1P1 antibody. In this study, to distinguish vascular tumors from histologic mimics using immunohistochemical means, we evaluated the expression of S1P1 in a range of vascular tumors. S1P1 expression was observed in eight of eight hemangiomas, four of four lymphangiomas, four of four epithelioid hemangioendotheliomas, three of three Kaposi’s sarcomas, and 15 of 15 angiosarcomas with vasoformative, spindle, epithelioid, and undifferentiated features. Conventional analysis and use of a tissue microarray of soft tissue tumors revealed three of 21 liposarcomas to have weak cytoplasmic staining and one of five squamous cell carcinomas to have membranous staining in a very limited area among 115 nonvascular tumors including histological mimics of angiosarcoma such as undifferentiated carcinoma, melanoma, and epithelioid sarcoma. The sensitivity with regards to the angiosarcoma cases was equal to, or even exceeded in undifferentiated angiosarcoma, that of CD31. Based on this study, S1P1 may be a useful adjunct to CD31 in cases where a vascular neoplasm requires a differential diagnosis.

Flocculent colloid in touch preparations of the thyroid.

凝集コロイドは正常甲状腺の濾胞内にしばしば観察されるが, その病態的意義は明らかにされていない. われわれは術中迅速診断のために提出された正常甲状腺19例*腺腫様甲状腺腫34例, 濾胞性腺腫7例, 濾胞癌4例, 乳頭癌28例, 髄様癌4例, 悪性リンパ腫1例, 未分化癌1例の組織片から捺印塗抹標本を作製し, 凝集コロイドの出現頻度や形態学的特徴を検討した. 凝集コロイドは5～60μ大で, 境界明瞭な, 円形, 楕円形, 三日月形, 多稜形, ヘルメット形など種々の形態を呈し, 背景に散在してみられた. 凝集コロイドの出現率は正常甲状腺47.4%, 腺腫様甲状腺腫14-7%, 濾胞性腺腫28.6%, 乳頭癌3.6%で, その他の疾患では観察されなかった. 甲状腺の捺印塗抹標本においては凝集コロイドの存在は良性疾患を示唆する指標になると思われた.

Colonic adenocarcinoma metastasizing to adenomatous goiter of the thyroid. Report of an autopsy case.

腺腫様甲状腺腫内に転移した大腸癌の1例を報告した. 患者は肝硬変と肝細胞癌を有する70歳, 女性で, 肝性昏睡のために死亡した. 剖検を行うと, 大腸と甲状腺の腺腫様甲状腺腫内に高円柱状異型細胞よりなる腺癌がみられた. その他の臓器には腺癌はみられなかった. 腺腫様甲状腺腫内腺癌の鑑別診断としてcolumnar cell variantの乳頭癌と大腸癌の転移が考えられた. 免疫組織化学的検索にて, 腺癌はCEAに陽性で, サイログロブリンに陰性であったことより, われわれは大腸癌が腺腫様甲状腺腫内に転移したと結論づけた. このような症例の鑑別診断においては免疫組織化学的検索が有用と思われた.

Thyroid papillary carcinoma associated with ossification. A feature of aspiration cytology.

骨形成を伴う甲状腺乳頭癌16例の穿刺吸引細胞診像を検討した. 正診率は47%で, 乳頭癌全体の正診率と比べかなり低かった. 骨化量が多い症例ほど腫瘍細胞の吸引が困難であったことより, 硬い腫瘤の穿刺吸引においては, たとえ陰性であっても良性と決めつけない方がよいと思われた. 全例において, 塗抹標本内には骨組織は認められなかった. 3例においては, 大小不同や泡沫状の胞体を有する脂肪細胞がみられ, 形態学的に乳頭癌組織内の骨梁間にみられる脂肪細胞に一致するため, そのような脂肪細胞は骨化を伴った乳頭癌の存在を間接的に示唆する所見と思われた.