Toshiyuki Ishige

Differentiation and apoptosis in pilomatrixoma.

We carried out a histopathologic study of pilomatrixoma, a benign skin tumor, and also examined apoptosis and hair differentiation with the aim to understand the presence of amorphous debris and cyst formation in the tumor. Among 16 cases of pilomatrixoma examined, 11 were at the early regressive stage and 5 were at the late regressive stage according to the classification by Kaddu et al. In the former cases, tumor nests were basically composed of basophilic, transitional, and shadow cells. Cyst formation was evident in all cases and squamoid epithelium was observed in 4 cases at the early regressive stage. Amorphous debris was found in all cases including those at the late regressive stage. Immunohistochemical analysis revealed positive reaction products for β-catenin and Lef-1 in basophilic and transitional cells, although their distribution differed. Immunoreactivity for β-catenin was observed in the lower transitional cells, whereas immunoreactivity for Lef-1 was also evident in the upper transitional cells. Positive reactions for hair keratins were found in the cytoplasm of transitional and shadow cells, but not in the amorphous debris. Examination by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method revealed positive reactions in transitional and some shadow cells. These results suggest that in pilomatrixoma, production of hair keratin and induction of apoptosis may occur at the same time, and that unlike the normal hair follicle irregular expression of β-catenin and Lef-1 results in the appearance of amorphous debris and cyst formation.

Overexpression of Activation-Induced Cytidine Deaminase in MTX- and Age-Related Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorders of the Head and Neck

Recent research has shown that activation-induced cytidine deaminase (AID) triggers somatic hypermutation and recombination, in turn contributing to lymphomagenesis. Such aberrant AID expression is seen in B-cell leukemia/lymphomas, including Burkitt lymphoma which is associated with c-myc translocation. Moreover, Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) increases genomic instability through early growth transcription response-1 (Egr-1) mediated upregulation of AID in B-cell lymphoma. However, few clinicopathological studies have focused on AID expression in lymphoproliferative disorders (LPDs). Therefore, we conducted an immunohistochemical study to investigate the relationship between AID and LMP-1 expression in LPDs (MTX-/Age-related EBV-associated), including diffuse large B-cell lymphomas (DLBCLs). More intense AID expression was detected in LPDs (89.5%) than in DLBCLs (20.0%), and the expression of LMP-1 and EBER was more intense in LPDs (68.4% and 94.7%) than in DLBCLs (10.0% and 20.0%). Furthermore, stronger Egr-1 expression was found in MTX/Age-EBV-LPDs (83.3%) than in DLBCLs (30.0%). AID expression was significantly constitutively overexpressed in LPDs as compared with DLBCLs. These results suggest that increased AID expression in LPDs may be one of the processes involved in lymphomagenesis, thereby further increasing the survival of genetically destabilized B-cells. AID expression may be a useful indicator for differentiation between LPDs and DLBCLs.

A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report

A subependymoma is a benign primary brain tumor classified as a World Health Organization grade I tumor; it is asymptomatic in most cases. We present the case of a 66-year-old Japanese man with a complaint of recurrent vomiting that led to the discovery of a large mass with hemorrhage, peritumoral edema, and a midline shift in the posterior horn of the right lateral ventricle. The patient was pathologically diagnosed with subependymoma after undergoing total tumor resection; a year after the surgery, he was free from tumor recurrence. Although symptomatic subependymomas are rare, they tend to show hemorrhage with peritumoral edema on neuroradiological tests and tend to be confused with high-grade brain tumors. In the present case, we highlight the importance of the appropriate diagnosis for subependymomas showing neuroradiological features that mimic high-grade gliomas. This diagnosis will help in providing suitable treatment for subependymomas.

Uterine corpus tumor with neuroectodermal differentiation and frequent ganglion-like cells in a postmenopausal woman

Highlights • Uterine neuroectodermal tumors (NETs) are uncommon malignant neoplasm with poor prognosis.• Ganglion-like cells with fibrillary background as major component of uterine NETs are extremely rare.• We present a patient affected by uterine NET with frequent ganglion-like cells, resembling ganglioneuroblastoma.• This case report is important to define the pathogenesis and establish better treatments for neuroectodermal tumors.

An autopsy case of hyperthyroid cardiomyopathy manifesting lethal congestive heart failure

To the Editor: Hyperthyroid cardiomyopathy is an acute life-threatening condition and requires immediate and emergent medical attention. Although cardiovascular disorders such as congestive heart failure (CHF) still have high mortality in thyroid storm conditions, histopathological features of the myocardium in patients with thyroid storm are poorly understood. Here, we report a rare autopsy case of hyperthyroid cardiomyopathy showing severe CHF superimposed on Graves’ disease. A 56-year-old Japanese male patient recognized exertional dyspnea 1 month before his death, and then he visited a general practitioner 6 days before. His chest X-ray revealed an enlarged heart with congestion of the lung and accumulation of bilateral pleural effusion, while his laboratory data indicated hyperthyroidism. Heart failure on thyroid storm was suspected, and he was transferred to our hospital 5 days before his death. There was no obvious past history of thyroid diseases. He was admitted to the emergency and critical care unit of our hospital due to pyrexia (39.5°C), rapid atrial fibrillation (AF, 120–150 bpm), CHF (class IV in the classification of the New York Heart Association) and diarrhea. Chest X-ray revealed congestive heart failure and blood tests showed high value of free T3 hormone (26.86 pgmL ) and free T4 hormone (7.77 ngmL ) accompanied by low value of thyroid-stimulating hormone (TSH; less than 0.01mIUmL ). A high value of antibodies to thyroperoxidase (145 IUmL ) and thyroglobulin (1600fold) were also identified. We diagnosed thyroid storm on Graves’ disease manifesting severe CHF. Accelerated heart rate and low blood pressure sustained despite treatment with propylthiouracil, potassium iodide, hydrocortisone, b-blocker, adrenalin and noradrenalin on the day. His collapsed hemodynamic state required the assistance of percutaneous cardiopulmonary support (PCPS) and intra-aortic balloon pump (IABP) 4 days before death. Progression of renal failure with hyperkalemia and acute liver failure (AST 13010 IU L , ALT 2093 IU L ) required hemodialysis and plasma exchange 3 days before death. In spite of our intensive care, he died of sepsis and multiple organ failure. An autopsy was performed under guidelines approved by the Nihon University Itabashi Hospital. The thyroid gland weighing 53 g (15–35 g of normal range) indicated diffuse enlargement (Fig. 1a). Microscopic observation showed follicular hyperplasia composed of columnar follicular epithelial cells with vacuolated colloid. Occasional papillary infolding of the epithelial cells was also observed. These findings suggested Graves’ hyperthyroidism. The enlarged heart weighed 450g due to the eccentric hypertrophy and dilation of both ventricles with serous pericardial effusion (75mL). No evidence of pericarditis was revealed by gross and histological examination. Transverse cut section of the heart revealed edematous and voluminous left ventricular (LV) wall (LV septal thickness1⁄4 16.5 mm) with dilatation of both ventricular cavities (LV maximum diameter1⁄4 52.0mm). Slight thickening of right ventricular wall was noted (RV maximum thickness1⁄4 6mm). Grayish appearance with disseminated reddish spots were identified on the cut surface before fixation (Fig. 1b). There was no valvular deformity and verruca, measuring tricuspid 13 cm, pulmonary 8.5 cm, mitral 11 cm and aortic 7.5 cm in circumference. Microscopically, left ventricular walls demonstrated marked congestion with dilatation of various sized vessels including capillaries and enhanced interstitial edema accompanied by atrophy of myocardium and lipofuscin granule deposition (Fig. 1c). Gross appearance of tiny reddish spots in the myocardium corresponded to the dilated mediumto large-sized vessels with congestion without hemorrhage. Stretched, thin and wavy myocardium was also observed (Fig. 1d). No morphological change was detected in conduction systems such as sinus node, atrioventricular node and His bundle. Atherosclerotic luminal narrowing up to 60% was found in the coronary arteries without fresh thrombus formation. An autopsy also revealed severe bronchopneumonia with histological evidence of disseminated intravascular coagulation (DIC), massive central hemorrhagic necrosis of liver (910 g), acute tubular necrosis of kidneys (260 g in left, and 270 g in right), ischemic colitis with ulceration, atrophy of adrenal glands with foci of hemorrhage and necrosis (10 g in left, and 12 g in right) and systemic congestion with ascites (900mL). As we have referred to the previously published literature, cardiac interstitial edema is also reported in some autopsy cases of hyperthyroid cardiomyopathy. Katsuyama described interstitial edema in subendocardium, dilation of capillaries and congestion in 6 autopsy cases. In the current case, marked dilation of capillaries with interstitial edema was observed in the overall locations of the myocardium. Furthermore, massive congestion of the lung with dilatation of the right ventricle suggested the presence

Successful pregnancy in a case of bladder and ovary endometriosis following cystoscopy‐assisted laparoscopic resection

A 34‐year‐old, gravida 0 para 0 Japanese woman visited a regional hospital complaining of dysmenorrhea, hematuria during menstruation, and right inguinal pain. She had a history of dysmenorrhea and three prior rounds of in vitro fertilization with embryo transfer, which were all with transfers of cryopreserved‐thawed single embryos in natural cycles, resulting in no pregnancy. An ultrasound revealed a large 2 × 1‐cm nodule between the bladder and the anterior wall of the uterus and a 3‐cm cystic lesion in the right adnexal area. A combined cystoscopic and laparoscopic resection of the bladder endometriosis and cystectomy of the right endometrioma were carried out. A single ultrasound‐guided transfer of a cryopreserved‐thawed embryo in the cleavage stage was performed 4 months postoperatively, which resulted in an uncomplicated pregnancy. The combined, single procedure was minimally invasive and eradicated the lesions that may have caused the infertility.