Mika Watanabe

Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo

Curcumin (diferuloylmethane) has chemopreventive and chemotherapeutic potentials against various types of cancers. We have developed a series of curcumin analogs to improve its low bioavailability by enhancing its potentials. The newly synthesized analog GO‐Y030 [(1E, 4E)‐1,5‐bis‐(3,5(‐bismethoxymethoxyphenyl) penta‐1,4‐dien‐3‐one] showed a 30‐fold greater growth suppression in vitro via similar molecular mechanisms to curcumin. The availability of this analog was examined by using a mouse model harboring the germ‐line mutation of Apc, Apc580D/+, in vivo. Apc580D/+ mice had a very limited survival time with an intestinal obstruction due to polyposis. The average tumor number in mice fed GO‐Y030 was reduced to 61.2% of those that were fed the basal diet (P < 0.05). Compared with Apc580D/+ mice fed the basal diet (median survival time = 166.5 days), a significantly prolonged lifespan (213 days) was observed in Apc580D/+ mice fed GO‐Y030. The chemopreventive effect with GO‐Y030 was improved, compared with curcumin (191 days). The survival benefit corresponded to the diminished intestinal tumor incidence in Apc580D/+ mice fed GO‐Y030. No adverse reactions were observed, judging from body weight or biochemical data concerning liver and renal damage. Degradation of accumulated β‐catenin with curcumin is one of the major mechanisms of chemoprevention in colorectal carcinogenesis. It was demonstrated that the number of β‐catenin‐positive adenoma cells in Apc580D/+ mice fed GO‐Y030 was reduced. (Cancer Sci 2009; 100: 956–960)

Predictive factors for overall and progression-free survival, and dissemination in oligodendroglial tumors

The pattern of recurrence and predictive factors for tumor progression, dissemination and survival in oligodendroglial tumors were investigated. 56 consecutive patients with oligodendroglial tumors were retrospectively analyzed to determine the predictive significance of various factors, including World Health Organization grade, loss of chromosomes 1p and 19q, and immunohistochemical features of TP53, O6-methylguanine-deoxyribonucleic-acid-methyltransferase, CD44H, nestin, and Ki-67. Eleven patients developed dissemination, and had significantly shorter post-progression survival compared to ten patients with local recurrence. Univariate analysis showed that retention of chromosome 1p or 19q, Ki-67 labeling index ≥xa025%, diffuse expression of nestin, and p53 labeling index ≥xa010% were unfavorable factors for overall, progression-free, and dissemination-free survival. Multivariate analysis showed that Ki-67 labeling index ≥xa025% and diffuse expression of nestin were significant for dissemination-free survival. In conclusion, post-progression survival shows significant differences between patients with local and disseminated recurrence. Ki-67 labeling index and nestin expression pattern are useful markers to predict dissemination.

Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma

The incidence of hemorrhagic onset in pilocytic astrocytoma and pilomyxoid astrocytoma, and the clinical and histological characteristics, were compared to other types of neuroepithelial tumors or nonhemorrhagic pilocytic astrocytoma by retrospective review of 445 consecutive neuroepithelial tumors treated at our institute. Hemorrhagic onset was observed in 4 of 35 (11.4%) patients with pilocytic astrocytoma and pilomyxoid astrocytoma, with higher incidence than in glioblastoma (3.9%), anaplastic oligodendroglioma (7.7%), and anaplastic ependymoma (7.1%). The hemorrhagic onset occurred in 2 patients with sporadic pilocytic astrocytoma, 1 with pilocytic astrocytoma associated with neurofibromatosis type 1, and 1 with pilomyxoid astrocytoma. There was no correlation between hemorrhagic onset and clinical features, including age, sex, tumor location, proliferative activity, or microvascular proliferation. Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma is not as uncommon as was previously thought, so pilocytic astrocytoma or pilomyxoid astrocytoma should be considered in the differential diagnosis of patients with brain tumors manifesting as hemorrhagic onset.

Usefulness of immunohistochemistry for differential diagnosis between benign and malignant breast lesions

Immunohistochemistry (IHC) is routinely performed during pathology practice for various breast lesions. Hormone receptor and HER2 analysis for primary breast carcinoma and cytokeratin staining for sentinel lymph nodes analysis are widely conducted. In addition to those markers, there are several situations in which certain IHC staining is valuable as an ancillary tool. This manuscript will present three useful examples of IHC for making differential diagnosis between benign and malignant lesions. Case 1 is an intraductal papilloma with solid epithelial proliferation, for which diagnosis was resolved by myoepithelial markers and high-molecular-weight cytokeratins (HMWCKs). Case 2 is a noninvasive ductal carcinoma with solid and papillary morphology. Many cases with such morphology mimic benign papillomas, but expression of neuroendocrine markers may lead to the correct diagnosis. Case 3 is a benign complex sclerosing lesion, with recognition of a pseudoinvasive process by myoepithelial markers. Although IHC results were excellent in these cases, they are effective only for limited situations. It is important to use IHC with caution, and re-evaluation of histological findings on hematoxylin and eosin stain and clinicopathological correlation of each case is essential.

Epithelioid Sarcoma-like Haemangioendothelioma: A Case Report

© 2009 The Authors. doi: 10.2340/00015555-0599 Journal Compilation

Application of high-definition flexible neuroendoscopic system to the treatment of primary pineal malignant B-cell lymphoma

BACKGROUNDnEndoscopic procedure for pineal region tumors and associated hydrocephalus has been getting more standard. We applied high-definition flexible neuroendoscopic system to the initial management of primary pineal malignant B-cell lymphoma. Efficacy of this new technology as an initial treatment of pineal region tumors is discussed.nnnCASE DESCRIPTIONnA 31-year-old man presented with progressive left abducens nerve palsy with headache and nausea. Magnetic resonance imaging showed multiple enhanced lesions in several cranial nerves and obstructive hydrocephalus due to a pineal cystic lesion with nodular enhancement on its roof. Diagnostic endoscopic biopsy of the pineal region tumor and ETV were performed using new flexible endoscopic system, in which a small CCD camera is implanted at the tip of the flexible scope, without complications. The thin cyst membrane was perforated and then opened with endoscopic forceps. A biopsy of the solid nodule on the cyst wall was carefully performed without injuring the surrounding venous system. We found a lot of small wartlike lesions along the third ventricular wall and fish egg-like abnormal lesions adhered to the colloid plexus around the pineal region, which were considered to be associated with dissemination. These lesions were not apparent in initial MRI. Histopathologic diagnosis of the pineal region tumor was malignant B-cell lymphoma.nnnCONCLUSIONnEndoscopic biopsy and ETV for pineal region tumors can be safely achieved using a high-definition flexible neuroendoscopic system. Moreover, this system allowed us to observe disseminated lesions that are not revealed by preoperative neuroradiologic studies, which might enable us to make staging diagnosis of the disease.

Pseudolymphomatous angiokeratoma: report of three cases and an immunohistological study

Background.u2002 Pseudolymphomatous angiokeratoma (PA), originally termed ‘acral pseudolymphomatous angiokeratoma of children’, is a disorder characterized clinically by development of red nodules on the extremities and histologically by a subepidermal dense lymphocyte infiltrate.

Multiple Bone Metastasis of Sclerosing Epithelioid Fibrosarcoma 12 Years after Initial Surgery—Increasing Ki-67 Labeling Index

Sclerosing epithelioid fibrosarcoma (SEF) is a rare sarcoma of low-grade malignancy. There has been no report to describe the comparison of histological features of SEF between primary and metastatic lesions in spite of high local recurrence rate. We report the histological changes and increasing Ki-67 labeling index of the primary and metastatic lesions of SEF. The patient was a 31-year-old man. At 18, a tumor in the abdominal wall was excised. At 23, the tumor recurred which was removed again. At 30, he was referred to our hospital because of swelling and pain in the chest. Histological examination of the chest wall tumor showed epithelioid cells arranged like alveolar pattern with dense collagen stroma. These findings were consistent with those of SEF. Abdominal and the rib tumors showed the same immunohistochemistrical expression. It is noteworthy that the tumor cells of the rib lesion showed increased cellularity, and its Ki-67 activity was higher as compared with the abdominal tumor, suggestive of progression of malignancy of SEF.

Neuro-endoscopic management of mesencephalic intraparenchymal cyst: a case report

BACKGROUNDnIntraparenchymal cyst of the mesencephalon is rare, and its natural course is unclear. The optimal treatment for this entity is still undetermined.nnnCASE DESCRIPTIONnA 54-year-old woman was found to have asymptomatic multilobulated mesencephalic cysts. Two years after the initial diagnosis, she experienced headache and double vision, when MRI showed the enlargement of the multilobulated cystic lesions which markedly compressed the mesencephalon and the aqueduct, resulting in noncommunicating hydrocephalus. She underwent diagnostic endoscopic biopsy and ETV by flexible endoscopic system, which revealed the mesensephalic cyst wall at the dorsal part of the third ventricle floor. A part of the cyst membrane was carefully excised by endoscopic forceps without injuring the surrounding structures. Histopathological examination revealed that the cyst wall was exclusively neuroglial tissue, and the presence of neoplasm was ruled out. Her symptoms were relieved immediately after surgery, and postoperative MRI showed both the shrinkage of mesencephalic cysts and the improvement of hydrocephalus. There is no recurrence of her symptoms, and MRI findings have been stable during the 3 year follow-up period.nnnCONCLUSIONnIntraparenchymal cysts of the mesencephalon have an expanding nature. Once those cysts become symptomatic, we recommend endoscopic procedure including decompression and biopsy of the cyst with ETV.

Collision tumor of anaplastic oligodendroglioma and gangliocytoma: a case report

A 53-year-old woman presented with a rare case of coexistence of anaplastic oligodendroglioma with gangliocytoma manifesting as progressive disturbance of consciousness and left hemiparesis. Magnetic resonance imaging with gadolinium demonstrated the mass lesion consisted of a strongly enhanced area around the middle cerebral artery and less enhanced areas in the right temporal lobe, insula, and basal ganglia. She underwent subtotal resection of the tumor, resulting in improvement of her symptoms. Macroscopic and histological examination showed the tumor consisted of two distinct components, grayish soft tissue and yellowish hard tissue. The former consisted of cells with equal-sized round-to-oval hyperchromatic nuclei and perinuclear halo with microvascular proliferation and necrosis, and the diagnosis was anaplastic oligodendroglioma. The latter consisted of large and dysplastic neurons with marked nucleoli and basophilic cytoplasm containing Nissl bodies, with nonneoplastic glial cells in the stroma, and the diagnosis was gangliocytoma. Both lesions were distinct, but intermingled at the border. These two tumors apparently occurred as a collision tumor.