Sohsuke Yamada

Peroxiredoxin 4 (PRDX4): Its critical in vivo roles in animal models of metabolic syndrome ranging from atherosclerosis to nonalcoholic fatty liver disease: PRDX4 in metabolic syndrome

The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal antioxidative function, is ubiquitously synthesized and abundantly identified in various organisms. In contrast to the intracellular localization of other family members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects against oxidative damage by scavenging reactive oxygen species in both the intracellular (especially the endoplasmic reticulum) compartments and the extracellular space. We generated unique human PRDX4 (hPRDX4) transgenic (Tg) mice on a C57BL/6J background and investigated the critical and diverse protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its role in the intestinal function in various animal models. Our published data have shown that PRDX4 helps prevent the progression of metabolic syndrome by reducing local and systemic oxidative stress and synergistically suppressing steatosis, inflammatory reactions, and/or apoptotic activity. These observations suggest that Tg mice may be a useful animal model for studying the relevance of oxidative stress on inflammation and the dysregulation of lipid/bile acid/glucose metabolism upon the progression of human metabolic syndrome, and that specific accelerators of PRDX4 may be useful as therapeutic agents for ameliorating various chronic inflammatory diseases.

Primary enteric-type tubulovillous adenocarcinoma arising in the renal pelvis: Letter to the Editor

To the Editor: In 1960, Hasebe et al. first demonstrated the clinicopathological features of an extremely rare case of primary mucinous adenocarcinoma arising in the renal pelvis. Following that, a substantial number of interesting case reports describing the pathological features of primary pelvic adenocarcinoma were published; however, within our thorough investigation, we found less than 100 cases reported in the English literature, with most cases reported from Asian countries. Indeed, it is well-known that transitional cell (urothelial) carcinoma accounts for up to 90% of epithelial-origin malignancies arising from the renal pelvis, whereas adenocarcinoma accounts for less than 1%. Pure adenocarcinomas of the renal pelvis are histopathologically classified as tubulovillous (71.5%), mucinous (21.5%), or papillary non-intestinal (7.0%). We herein report an extremely rare case of primary enteric-type tubulovillous adenocarcinoma arising in the markedly dilated left renal pelvis, presenting as hemorrhagic, necrotic and mucinous neoplasms, in a background of severe hydrocalycosis and hydroureter. The patient, who was a man in his early seventies with an unremarkable previous medical history, presented with gross hematuria, lumbago and back pain. CT revealed severe hydronephrosis in the left kidney, associated with two renal pelvic calculi and occupying heterogeneouslyenhanced multiple pelvic nodular lesions. However, there was no definite evidence of other tumor lesions of the neck, chest, or abdomen, including metastatic foci in the lymph nodes or other organs. The laboratory data, including the blood cell count, chemistry and tumor marker levels, were within the normal limits, with the exception of mildly elevated CRP (0.43mg/dL) and uric acid (8.1mg/dL) levels. A urinalysis revealed a low white blood cell count (1 to 4 cells per high-power field). Based on the clinical findings, the initial diagnosis by the urologists was renal pelvic urothelial carcinoma with hydronephrosis and pelvic calculi; but, the urine cytology did not suggest malignancy. However, since the possibility of malignancy could not be excluded, left nephrouretectomy was performed. On gross examination, the left kidney, measured 20 13 cm and weighed 877g. Its cut surface (Fig. 1a) showed an overtly cystically-dilated renal pelvis, filled with pelvic calculi, and papillary-projected huge mass lesions, measuring more than 5 to 7 cm in diameter, which appeared gray-whitish in color, accompanied by frequent hemorrhage, necrosis and mucin production. This hydrocalycotic and hydroureteric kidney showed a markedly thinned pre-existing renal parenchyma (Fig. 1a). Our thorough examination revealed no anomalous findings (i.e., horseshoe kidney). A microscopic examination of these tumors demonstrated a proliferation of atypical tall columnar epithelial cells, arranged predominantly in a papillary or villoglandular or fused tubular growth pattern with mucin production and focal stromal invasion (Fig. 1b). On a high-power view, these atypical cells showed enlarged hyperchromatic nuclei, prominent nucleoli and abundant eosinophilic to clear cytoplasm with characteristic brush borders (Fig. 1d). Intriguingly, in the adjacent noncancerous renal pelvic mucosa, we occasionally recognized glandular metaplasia with mild cellular atypia in the covering urothelial epithelium (Fig. 1d). In contrast, our thorough investigation revealed no apparent adenomatous components. The markedly atrophic pre-existing kidney contained a very small number of glomeruli and uriniferous tubules embedded in prominent fibrosis. Very few inflammatory cells were observed. Immunohistochemistry revealed that the abovementioned enteric-type adenocarcinoma cells were specifically positive for CK7, CK20, CDX2, b-catenin and MUC2, and focally positive for MUC5AC. As to the bcatenin, the immunoreactivity uniquely showed a membranous—but not nuclear—staining pattern (Fig. 1e). Based on all of these features, the final diagnosis was primary enteric-type tubulovillous adenocarcinoma arising in the left renal pelvis. We hypothesized that this was possibly induced by a long-term inflammatory reaction caused by the patients pelvic calculi and/or hydrocalycosis/hydroureter. To date, the patient has been followed for approximately 2 years since surgery, and remains well without any sign of recurrence. Figure 1F shows a schematic illustration of the primary pelvic adenocarcinoma observed in the present case, which involved and extended to the hydrocalycotic and hydroureteric kidney with pelvic calculi. Aggressive surgical treatment in the early stage of primary renal pelvic adenocarcinoma might be associated with a better prognosis, as this disease is associated with higher-grade (i.e., invasive characteristics) malignant tumors, with a reported overall survival rate of <50% within 2 years after surgery. It is therefore critical to establish an accurate pre-operative diagnosis based on urine cytology, the clinical utility of which has been generalized in the diagnosis of urinary tract tumors. However, there are few reports of the cytological findings of primary renal pelvic

A Surgical Case of Venous Aneurysm of the Cephalic Vein with Unique Clinicopathological Findings for Venous Dissection: A Possible New Entity

We presented an extremely rare case of a 38-year-old female’s venous aneurysm of left cephalic vein with unique histopathological features, displaying variably thinned medial wall with focal, markedly reduced or absent smooth muscle cells and elastic fibers, most likely leading to the venous dissection with an intimal tear and many medial blood-filled vascular channels. We propose that those venous dissection-like findings would be a new feature especially from the clinicopathological viewpoints and might be considered in the classification of venous aneurysm. Further prospective studies are needed to validate the presence and significance of venous dissecting aneurysm as a new histopathological entity, after collecting and investigating a larger number of venous aneurysm cases examined. This short report could interest the scientific community, taken together with potentially specific findings of new entity, venous dissecting aneurysm.

FDG-PET/CT and diffusion-weighted imaging for resected lung cancer: correlation of maximum standardized uptake value and apparent diffusion coefficient value with prognostic factors

Diffusion-weighted magnetic resonance imaging (DWI) is useful for detecting malignant tumors and the assessment of lymph nodes, as FDG-PET/CT is. But it is not clear how DWI influences the prognosis of lung cancer patients. The focus of this study is to evaluate the correlations between maximum standardized uptake value (SUVmax) of FDG-PET/CT and apparent diffusion coefficient (ADC) value of DWI with known prognostic factors in resected lung cancer. A total of 227 patients with resected lung cancers were enrolled in this study. FEG-PET/CT and DWI were performed in each patient before surgery. There were 168 patients with adenocarcinoma, 44 patients with squamous cell carcinoma, and 15 patients with other cell types. SUVmax was a factor that was correlated to T factor, N factor, or cell differentiation. ADC of lung cancer was a factor that was not correlated to T factor, or N factor. There was a significantly weak inverse relationship between SUVmax and ADC (Correlation coefficient ru2009=u2009−xa00.227). In analysis of survival, there were significant differences between the categories of sex, age, pT factor, pN factor, cell differentiation, cell type, and SUVmax. Univariate analysis revealed that SUVmax, pN factor, age, cell differentiation, cell type, sex, and pT factor were significant factors. Multivariate analysis revealed that SUVmax and pN factor were independent significant prognostic factors. SUVmax was a significant prognostic factor that is correlated to T factor, N factor, or cell differentiation, but ADC was not. SUVmax may be more useful for predicting the prognosis of lung cancer than ADC values.

The clinicopathological comparison among nodal cases of idiopathic multicentric Castleman disease with and without TAFRO syndrome

Multicentric Castleman disease (MCD) is a systemic inflammatory disease potentially caused by an increase in the serum interleukin-6 (IL-6) level. Idiopathic MCD (iMCD) is histopathologically classified into three types: plasmacytic (PC), mixed, and hypervascular (hyperV) types. Recently, a unique clinical phenotype with a poor prognosis overlap with iMCD, thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis, and organomegaly (TAFRO syndrome), has been reported from Japan, but its detailed clinicopathological features remain unclear. In this study, we performed a clinicopathological analysis of 70 nodal cases of iMCD with and without TAFRO syndrome (nu202f=u202f37 versus nu202f=u202f33). Compared with iMCD without TAFRO, iMCD with TAFRO showed more atrophic lymphoid follicles (LF), greater distances between follicles, increased glomeruloid vascular proliferation within the germinal center, and increased follicular dendritic cells. In addition, the hyperV type in particular demonstrated severe atrophic LF and interfollicular vascular proliferation. Among the mixed-type cases, the serum IL-6 levels in iMCD with TAFRO were significantly higher than those in iMCD without TAFRO. Furthermore, compared to iMCD without TAFRO, the numbers of immunoglobulin G4 (IgG4)-positive and CD38-positive plasma cells were significantly decreased in iMCD with TAFRO.

An autopsy case of peripheral T cell lymphoma occurring in a postpartum woman: a unique case suggesting changes in the immunocharacteristics of lymphoma cells before and after delivery

BackgroundThe occurrence of malignant lymphoma after delivery is an extremely rare event. Although several cases of Hodgkin lymphoma and B cell lymphoma and a few cases of peripheral T cell lymphoma (PTCL) after delivery have been reported, there are no report of autopsy cases of PTCL in the puerperal period.Case presentationA 32-year-old Japanese woman with a past medical history of atopic dermatitis and bronchial asthma presented with generalized eruptions four days after the delivery of her first child; generalized skin induration and lymphadenopathy subsequently emerged. A skin biopsy specimen showed the diffuse proliferation of atypical lymphoid cells that were immunohistochemically-positive for CD4 but negative for CD8. She was diagnosed as PTCL, not otherwise specified (PTCL, NOS). She died one year and three months after the onset of symptoms. At autopsy, the systemic infiltration of lymphoma cells into the whole body was observed. Unexpectedly, these lymphoma cells were immuno-reactive with CD8 but not with CD4.ConclusionThe occurrence and development of PTCL after delivery with the shift from CD4 positivity to CD8 positivity may be associated with not only the selection of resistant subclone as a result of chemotherapy but also the changes of immune status before and after delivery.

Cytopathological findings of proliferating pilomatricoma misdiagnosed as a malignant parotid gland tumor

BackgroundPilomatricoma is a relatively common benign cutaneous adnexal neoplasm with differentiation towards the hair matrix, inner sheath of hair follicle and hair cortex. Proliferating pilomatricoma is a rare variant of pilomatricoma that can rapidly increase and may be misidentified as a malignant tumor. We herein report the cytopathological findings of proliferating pilomatricoma misdiagnosed as a malignant parotid tumor.Case presentationA 64-year-old man noticed an acne-like nodule in the left parotid region. It was painless, but it increased to a maximum diameter of 4.5xa0cm over 2xa0years. Clinically, left parotid gland carcinoma was suspected, and fine-needle aspiration cytology was performed. Clusters of epithelial cells were observed in a necrotic background, and malignant epithelial cells derived from salivary glands were suspected. Histologically, the resected tumor was diagnosed as proliferating pilomatricoma composed of basophilic cells and shadow cells apart from the parotid gland. However, on a re-evaluation of the cytological specimens, the irregular-shaped epithelial cells were considered to be from basophilic cells. Shadow cells with nuclear disappearance were also confirmed. Tumor recurrence and metastasis have not been observed in the four years since surgery.ConclusionThe present case was first interpreted as a malignant parotid gland tumor, but it was actually a benign skin appendage tumor. Pilomatricoma sometimes rapidly increases and may be mistaken for a malignant tumor. Although it is critical to recognize not only basophilic cells but also shadow cells, it cannot be diagnosed by cytological findings. The final diagnosis should be made on excision specimen only.

Two Surgical Cases of Combined Hepatocellular-Cholangiocarcinoma, Intermediate-Cell Subtype: Potentially Characteristic Gross Features

We herein reported two rare surgical cases of primary combined hepatocellular-cholangiocellular carcinoma, intermediate-cell subtype (CHC-INT), showing potentially characteristic and specific gross findings on their cut surface: both CHC-INTs demonstrated poorly demarcated and expansive and/or infiltrative hepatic nodules in lobulated margins, appearing clearly whitish in color. We were finally able to accurately diagnose the current lesions after thorough analyses including an appropriate and wide panel of immunohistochemical antibodies. Despite that, all pathologists should be aware that the potentially characteristic gross features of primary CHC-INT might also be one of the powerful supplementary tools for reaching its correct, conclusive diagnosis.

Tubulocystic Carcinoma of the Bile Duct

Tubulocystic carcinoma of the bile duct is extremely rare and has not been reported in the literature. We reported a case of cystic neoplasm of the liver with distinct histopathological features that could not be clearly classified as of either mucinous or intraductal papillary neoplasm. A 68-year-old Japanese patient had a multicystic biliary tumor within the liver. This tumor was detected on follow-up of polymyalgia rheumatica. The exophytic, multicystic, 35 × 50u2009mm mass was composed of complex tubulocystic structures. We initially suspected cystadenocarcinoma of the liver and performed radical operation. However, pathology ultimately showed it to be very rare tubulocystic carcinoma that derived from the bile duct. We reviewed the literature and describe the process of our differential diagnosis.