Hideki Orikasa

Immunohistochemical detection of human small lymphatic vessels under normal and pathological conditions using the LYVE-1 antibody.

The spread of tumor cells via lymphatic vessels to the lymph nodes is an important indicator of malignancy. However, previous markers used to identify lymphatic endothelium gave ambiguous results in immunohistochemical analyses with paraffin-embedded tissues. In this study, we attempted to prepare a polyclonal antibody against human lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) for detecting lymphatic vessels using immunohistochemistry. The antibody was raised against a region near the transmembrane anchor of LYVE-1 in New Zealand white rabbits. Immunostainings with anti-LYVE-1 and von Willebrand factor antibodies were performed in various normal and pathological tissues. LYVE-1 expression was confined to the endothelial surface of lymphatic vessels but was not found in the endothelium of blood vessels, which were positive for von Willebrand factor. Our LYVE-1 polyclonal antibody was useful for the identification of small lymphatic vessels in normal human tissues. In addition, the immunostaining enabled us to distinguish lymphatic invasion by malignant tumor cells from blood vessel invasion using paraffin-embedded sections. In conclusion, our polyclonal antibody against the transmembrane anchor of the peptide can be used to detect human lymphatic vessels under various conditions.

Trichilemmal cyst in the pulp of the index finger: a case report.

We reported a case of trichilemmal cyst in the pulp of the index finger. Histopathological features and unusual MR images are discussed.

Postmortem diagnosis of Fabry disease with acromegaly and a unique vasculopathy

A 44-year-old Japanese man with elevated growth hormone levels and gradual deterioration of mental and renal function was admitted to the hospital. With his deteriorated general condition and renal failure, the patient developed pulmonary thromboembolism and died of respiratory failure. Autopsy examination was conducted, which revealed abnormal accumulation or intracytoplasmic storage of lipid-rich material in the small blood vessels, kidney, heart, and nervous system. After postmortem pathologic studies, including light-microscopic histochemistry, electron microscopy, and biochemical analysis of the stored lipid contents, a final diagnosis of Fabry disease was made. Histopathologic examination revealed a unique vasculopathy characterized by the presence of abnormal intracytoplasmic lipid inclusions and vascular remodeling. With regard to the clinical presentation of acromegaly, hyperplasia but not adenomatous transformation of the acidophils of the anterior pituitary gland with immunohistochemical detection of growth hormone within the cells was noted. In this case, the complication of acromegaly with hyperplasia of the acidophilic cells of the anterior pituitary gland and the unique vasculopathy causing significant organ failure, mainly of the kidney, heart, and central nervous systems, possibly as a result of microcirculatory failure, are considered to be not incidental findings but to be intimately involved in the pathogenesis of Farby disease.

Atypical thymoma (WHO B3) with neuroendocrine differentiation : report of a case

We report a case of type-B3 thymoma manifesting neuroendocrine differentiation. The patient was a 42-year-old woman who complained of shoulder pain but had no symptoms of myasthenia gravis or anemia. The tumor was located in the anterior mediastinum and had directly invaded the pericardium and left lung. Histological examination revealed that the tumor was lobulated by bands of fibrous tissue, perivascular spaces were scattered throughout the tumor, and there were a few intraepithelial lymphocytes. The vast majority of lymphocytes in the perivascular spaces and in the lobulated tumor were immunohistochemically positive for TdT, MIC2, and CD1a. The majority of tumor cells were polygonal and medium or large in size. The tumor cells were weakly positive for synaptophysin, chromogranin A, CD56, and NSE. Small nests of small, relatively uniform polygonal cells were observed facing the fibrous bands. These cells resembled the cells of carcinoid tumors and were strongly positive for NSE, synaptophysin, chromogranin A, and CD56. Ultrastructurally, sparse dense-core granules were observed in the cytoplasm of a few tumor cells. This is a unique case of thymoma with neuroendocrine differentiation, and to the best of our knowledge this is the first such case ever reported.

An ultrastructural and immunohistochemical study of a combined submucosal granular cell tumor and lipoma of the colon showing a unique nodule-in-nodule structure: putative implication of CD34 or prominin-2-positive stromal cells in its histopathogenesis.

Dear Editor We recently had a patient with a unique combination of a granular cell tumor and a lipoma of the colon showing a nodule-in-nodule appearance by histopathological examination. Our patient, a 55-year-old Japanese man, underwent colonoscopic examination as part of a routine health check. Awhitish, polypoid lesion was found in the cecum (Fig. 1a, inset). Benign, submucosal tumor, such as a carcinoid tumor or a lipoma, was suspected and the lesion was resected endoscopically. The excised specimen measured 9×6 mm in size (Fig. 1a, inset). Low-power light microscopic examination of the tumor revealed nodular proliferation of mature fat cells in the submucosal layer of the colon (Fig. 1a) without a definitive fibrous capsule. In the proliferative submucosal lipomatous nodule, a cluster of small fibrous granular cell tumors was sitting upon the lipoma nodule beneath the slightly thickened layer of the muscularis mucosa (Fig. 1a), forming a nodule-in-nodule (a granular cell tumor nodule in a lipoma nodule) structure (Fig. 1a). In the smaller granular cell tumor nodule, tumor cells with rich, finely granulated, clear cytoplasm formed cell nests in an alveolar or fasciculated pattern, sometimes in proximity to bundles of peripheral nerve fibers (Fig. 1b). Dense fibrous collagen, spindle-shaped or stellate stromal cells, and some small vasculature blood vessels were seen in the extracellular stromal tissue of the granular cell tumor (Fig. 1b). The boundary between the granular cell tumor and the lipoma tissue was not well defined, which consisted of mixed intervening fibrous stroma containing abundant spindleshaped or stellate stromal cells (Fig. 1b). Most of the immunohistochemical characteristics were consistent with many previous literal descriptions of the immunohistochemical characteristics of granular cell tumors and lipomas. Briefly, negative controls were prepared by substituting the primary antibodies with nonimmunune immunoglobulin G. External organs served as positive controls. CD34 was expressed in endothelial cells, and prominin-2 was expressed in normal epithelial cells of the adult kidney and digestive tract. The granular cell tumor cells expressed various neurogenic markers of Schwann cells, including S-100, neuron-specific enolase, and CD56. Other neurogenic markers characteristic of neurons or neuroendocrine cells were also faintly positive, e.g., synaptophysin and chromogranins. Strong expression of markers of phagosomes or phagocytes (CD68) was also detected in the cells of the granular cell tumor component. Positive expression of CD34 was observed not only in the endothelial cells of the small vasculature, but also in the spindle-shaped or stellate stromal cells. Spindle-shaped or stellate stromal cells showing positive immunohistochemical staining for CD34 and/or prominin-2 were more conspicuous in the tumor nodules than other nontumorous areas of the colonic wall. (Fig. 1a). However, no expression of c-kit, myogenic cell markers (e.g. alpha smooth muscle actin, muscle actin of HHF35, desmin, and MEF-2), and CD10 was observed in the spindle-shaped or stellate stromal cells. A few spindle-shaped or stellate stromal cells among the cell nests of granular cell tumor were labeled by the antiprominin-2 antibody (Fig. 1c). Ultrastructual examination of the granular cell tumor tissue specimens by transmission electron microscope revealed alveolar aggregations of granular cell tumor cells with rather clear cytoplasm demarcated by thin T. Mori . H. Orikasa . K. Yamazaki (*) Department of Pathology, Saiseikai Central Hospital, l-4-17, Minatoku, Tokyo, 108-0073, Japan e-mail: KazutoYamazaki@aol.com Tel.: +81-3-34518211 Fax: +81-3-34577949

Anaplastic plasmacytoma with malignant pleural effusion lacking evidence of monoclonal gammopathy.

A case of plasmacytoma of the pleural cavity is reported with massive malignant pleural effusion, which, most unusually, lacked monoclonal gammopathy, thereby making it difficult to distinguish from lymphoma. The pleural tumor and pleural effusion contained large mononuclear lymphoma-like cells with distinct nucleoli. Immunohistochemistry revealed neither lymphoma markers nor clonal cytoplasmic nor cell surface immunoglobulins. Tumor cells were stained with vimentin and the plasma cell markers, VS38c, CD138 (syndecan-1), and MUM1 antibodies. Bone marrow contained small amounts of tumor consisting of similar cells. Electron microscopy showed well developed rough endoplasmic reticulum and peripherally positioned nuclei with euchromatin. Flow cytometry of bone marrow revealed a minimal involvement of CD38-positive cells. Chromosomal analysis of marrow cells revealed a complex abnormal karyotype. A polymerase chain reaction demonstrated clonal re-arrangement of the immunoglobulin heavy-chain gene. The overall results indicate a clonal expansion of tumor cells with primitive plasma cell differentiation with the highly unusual feature of absent monotypic immunoglobulin. The study illustrates the need for a comprehensive array of techniques to distinguish such rare non-synthesizing and non-secretory plasmacytomas from lymphoma.

Early Gastric Cancer Associated with Submucosal Heterotopic Gastric Glands, Preoperatively Diagnosed as Advanced Stage

症例は56歳の男性. 検診で指摘された胃の隆起性病変の精査および加療目的にて当科紹介となった. 胃体上～中部後壁小彎寄りにIIc様陥凹から広範に広がる粘膜下腫瘍様の隆起性病変を認め, 生検結果は高分化型腺癌であった. 術前診断はIIa+IIc様進行胃癌とし, 幽門側胃切除術を施行した. 病理学的検索の結果, 表層の高分化型管状腺癌(IIc+III, 1.5×1.5cm, sm)とその直下の粘膜下層に2.5×2.5cm大, 厚さ5mm前後の/胞状拡張の目立つ異所腺を認めた. 本症は本来胃粘膜固有層内にあるべき胃腺組織が異所性に粘膜下に認められるものであり, 発生原因としては後天性炎症説が有力視されている. 癌との関連性については諸説があり, 更なる症例検討の余地がある. 胃粘膜下異所腺が合併した早期胃癌病変であったため, 肉眼形態が修飾される形となり, 術前進行癌が疑われた1例について若干の文献的考察を加えて報告する.