Tohru Harada

Evaluation of new monoclonal anti-MyoD1 and anti-myogenin antibodies for the diagnosis of rhabdomyosarcoma.

New monoclonal anti‐MyoD1 and anti‐myogenin antibodies were evaluated immunohistochemically to determine whether they are useful in discriminating rhabdomyosarcoma (RMS) from other soft tissue tumors in routinely processed sections. Neither MyoD1 nor myogenin was expressed in normal, mature striated muscle. In RMS, nuclear expression of MyoD1 and myogenin was found in 82 and 80% of non‐overlapping cases, respectively. MyoD1 was generally expressed in small, primitive tumor cells, and larger cells exhibiting morphological evidence of skeletal muscle differentiation failed to express positive nuclear immunostaining. Positive nuclear staining for myogenin was stronger than that for MyoD1 in cases with abundant differentiated tumor cells, but was less prominent in cases in which small, primitive tumor cells predominated. No leiomyosarcomas, Ewing’s sarcomas/peripheral primitive neuroectodermal tumors or other soft tissue tumors exhibited nuclear expression of MyoD1 or myogenin. In conclusion, both anti‐MyoD1 and anti‐myogenin antibodies are useful for diagnosing RMS and for discriminating RMS from other soft tissue tumors.

Penile verrucous carcinoma with anaplastic transformation following radiotherapy. A case report with human papillomavirus typing and flow cytometric DNA studies.

We report a case of penile verrucous carcinoma with anaplastic transformation after radiotherapy. A 49-year-old man with penile verrucous carcinoma initially underwent excision and chemotherapy followed by radiotherapy when the carcinoma recurred locally. Twenty-four months after the completion of radiotherapy, the verrucous cancer transformed to an anaplastic spindle-cell carcinoma, which resulted in his death 10 months after diagnosis. Autopsy confirmed a huge hemorrhagic recurrent lesion and lung metastases. In situ hybridization with biotinylated DNA probes did not detect any type of human papillomavirus (HPV) (types 6/11, 16/18, and 31/33/51) in either the primary or the anaplastic tumor. Immunohistochemical HPV capsid antigens were also negative in both lesions. A flow cytometric analysis, using paraffin-embedded materials, showed a diploid DNA content in the excised verrucous carcinoma and an aneuploid content in the anaplastic tumor. This patient most likely had radiation-induced transformation of an anaplastic carcinoma. Wide excision and, if necessary, amputation, are preferred to radiotherapy.

Expression of SGLT1 in Human Hearts and Impairment of Cardiac Glucose Uptake by Phlorizin during Ischemia-Reperfusion Injury in Mice

Objective Sodium-glucose cotransporter 1 (SGLT1) is thought to be expressed in the heart as the dominant isoform of cardiac SGLT, although more information is required to delineate the subtypes of SGLTs in human hearts. Moreover, the functional role of SGLTs in the heart remains to be fully elucidated. We herein investigated whether SGLT1 is expressed in human hearts and whether SGLTs significantly contribute to cardiac energy metabolism during ischemia-reperfusion injury (IRI) via enhanced glucose utilization in mice. Methods and Results We determined that SGLT1 was highly expressed in both human autopsied hearts and murine perfused hearts, as assessed by immunostaining and immunoblotting with membrane fractionation. To test the functional significance of the substantial expression of SGLTs in the heart, we studied the effects of a non-selective SGLT inhibitor, phlorizin, on the baseline cardiac function and its response to ischemia-reperfusion using the murine Langendorff model. Although phlorizin perfusion did not affect baseline cardiac function, its administration during IRI significantly impaired the recovery in left ventricular contractions and rate pressure product, associated with an increased infarct size, as demonstrated by triphenyltetrazolium chloride staining and creatine phosphokinase activity released into the perfusate. The onset of ischemic contracture, which indicates the initiation of ATP depletion in myocardium, was earlier with phlorizin. Consistent with this finding, there was a significant decrease in the tissue ATP content associated with reductions in glucose uptake, as well as lactate output (indicating glycolytic flux), during ischemia-reperfusion in the phlorizin-perfused hearts. Conclusions Cardiac SGLTs, possibly SGLT1 in particular, appear to provide an important protective mechanism against IRI by replenishing ATP stores in ischemic cardiac tissues via enhancing availability of glucose. The present findings provide new insight into the significant role of SGLTs in optimizing cardiac energy metabolism, at least during the acute phase of IRI.

Pigmented Perivascular Epithelioid Cell Tumor of the Kidney

A case of pigmented perivascular epithelioid cell tumor of the kidney in a 57-year-old woman with a clinically indicated tuberous sclerosis is presented. The lesion was a 3.0-cm, well-demarcated, black-colored mass. The tumor was histologically characterized by an epithelioid arrangement of round to polygonal cells with round nuclei and clear cytoplasm containing abundant melanin. Tumor cells showed mild atypia and low mitotic activity. A spindle cell proliferation was focally observed. There were no adipose elements or thick-walled vascular vessels. The stroma demonstrated intervening, thin, fibrovascular septa. Immunohistochemically, the tumor cells were strongly positive for HMB-45 but negative for epithelial and muscle markers, vimentin, and S100 protein. The patient had no evidence of disease 3 months after surgery. Pathologists and clinicians should know about the existence of pigmented perivascular epithelioid cell tumor of the kidney. This type of tumor should be differentiated from clear cell renal cell carcinoma or malignant melanoma.

A case of pulmonary lymphangioleiomyomatosis complicated with uterine and retroperitoneal tumors

A 39-year-old female experienced dyspnea on exertion for eight months. Chest CT demonstrated findings of Lymphangioleiomyomatosis (LAM), including diffuse thin-walled cystic lesions. A surgical lung biopsy revealed human melanoma black-45-positive cell infiltration and aggregation, resulting in a diagnosis of sporadic LAM without tuberous sclerosis complex. Pelvic MRI showed two large tumors, one of which was in the myometrium and the other was in the retroperitoneal space. Because we were not able to exclude the presence of malignant tumors using MR imaging, the tumors were surgically resected. The histopathology demonstrated the resected tumors to be composed of LAM cells. The patients symptoms worsened, and sirolimus was administered, which improved the dyspnea and pulmonary function. The adverse effect was mild liver damage. Following the initiation of treatment with sirolimus, transient elevation of the serum KL-6 level was detected without interstitial pneumonia. This LAM case complicated with large uterine and retroperitoneal tumors was successfully treated with surgical resection and sirolimus.

Yolk sac tumour of the ear

We report the second known case of yolk sac tumour of the external auditory canal, occurring in an eight‐month‐old girl. The excised tumour demonstrated histopathological and immunohistochemical features identical to those of yolk sac tumours of gonadal origin. The tumour was aneuploid by flow cytometry. The patient received chemotherapy post‐operatively and has had no evidence of disease 13 months after surgery.

Histopathologically Proven Autoimmune Pancreatitis Mimicking Neuroendocrine Tumor or Pancreatic Cancer

Autoimmune pancreatitis (AIP) can be difficult to distinguish from pancreatic cancer. We report a case of histopathologically proven AIP mimicking neuroendocrine tumor (NET) or pancreatic cancer in a 53-year-old man. He was referred to our hospital for further evaluation of a pancreatic mass detected on ultrasonography at a medical check-up. Abdominal ultrasonography showed a 15-mm hypoechoic mass located in the pancreatic body. Computed tomography revealed a tumor without any contrast enhancement, and magnetic resonance imaging demonstrated the mass to be hyperintense on diffusion-weighted image. Endoscopic retrograde cholangiopancreatography revealed slight dilatation of a branch of the pancreatic duct without stricture of the main pancreatic duct. The common bile duct seemed intact. Under suspicion of a non-functioning NET or malignant neoplasm, laparotomy was performed. At laparotomy, an elastic firm and well-circumscribed mass was found suggestive of a non-functioning NET, thus enucleation was performed. Histopathologically, the lesion corresponded to AIP.

Aggregation and phosphorylation of α-synuclein with proteinase K-resistance in focal α-synucleinopathy predominantly localized to the cardiac sympathetic nervous system

Aggregates of α-synuclein, a major component of Lewy bodies (LBs) and Lewy neurites (LNs), are distributed throughout the nervous system, including the central nervous system (CNS), sympathetic ganglia, enteric nervous system (ENS), cardiac and pelvic plexuses, submandibular gland, adrenal medulla and skin, in incidental Lewy body disease (ILBD), Parkinsons disease (PD), dementia with Lewy bodies (DLB), and pure autonomic failure (PAF) [1-3]. Here we report focal α-synucleinopathy predominantly localized to the cardiac sympathetic nervous system (SNS). Aggregation and phosphorylation of α-synuclein with proteinase K (PK)-resistance developed predominantly in the cytoplasm and proximal axon of the postganglionic sympathetic neuron (PGSN). This article is protected by copyright. All rights reserved.

Histological reassessment of the role of bridging fibrosis in the angioarchitectural features associated with lobular distortion of the liver in chronic viral hepatitis

To reassess the role of bridging fibrosis in the lobular distortion of the liver from an angioarchitectural aspect.

A Case of Glomus Tumor of the Stomach Resected by Laparoscopic Surgery - A Case Report.

症例は62歳の男性. 検診の上部消化管造影検査の際胃の異常陰影を指摘され当院外来を受診した. 身体所見, 血液検査では異常所見は認められなかった. 上部消化管造影検査では幽門前庭部小彎に2.5cm大の立ち上がりなだらかで表面平滑な隆起性病変を認め, 超音波内視鏡検査 (EUS) では筋層内の均一な低エコーの腫瘍と描出され, 胃平滑筋腫の疑いと診断された. 生検ではGroup 1であった. 確定診断と治療を兼ね腹腔鏡下胃部分切除術を行った. 病理組織学的には腫瘍細胞は固有筋層内に存在し, 卵円形, 均一で広い胞体を有し胃glomus腫瘍と診断した.胃glomus腫瘍は1962年に本邦で初めて報告されて以来69例しか報告例のないまれな疾患である. 腹腔鏡下に切除した報告例は過去1例だけであるが, 良性腫瘍である胃glomus腫瘍に対する治療法としては腹腔鏡下胃部分切除が妥当であると考える.