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An 80-year-old woman was found to have a 40-mm depressed-type gastric cancer. Computed tomography showed multiple lymph node enlargement, including paraaortic lymph nodes. The extent of lymph node enlargement was significant compared with the depth of the primary lesion. We conducted distal gastrectomy, D2 lymph node dissection, and a paraaortic lymph node biopsy. Microscopically, the tumor was diagnosed as mucosal cancer. In the dissected lymph nodes, noncaseating granuloma was found without metastasis of adenocarcinoma. Immunohistochemical staining using Propionibacterium acnes-specific antibodies showed a large number of P. acnes-positive cells in the granulomas. Finally, the tumor was diagnosed as early-stage gastric cancer and sarcoidosis.

An 80-year-old woman presented with a 30-mm protruding lesion-like submucosal tumor with a central depression located at the anterior wall of the upper gastric body. The depressed area had a well-demarcated margin, while the other area was covered by a non-neoplastic mucosa. A biopsy specimen revealed neuroendocrine carcinoma. Endoscopic ultrasonography revealed a heterogeneous mass with a clearly distinguished border in the submucosal layer. The mass had two distinct areas adjacent to each other. In addition, a hypoechoic zone was observed on the margin of the mass. Distal gastrectomy was performed. The final diagnosis was a mixed neuroendocrine-non-neuroendocrine neoplasm arising from the heterotopic gastric gland.

A 73-year-old man was initially diagnosed with a 50-mm, depressed-type early gastric cancer on the anterior wall of the angulus, and the lesion was curatively resected en bloc by endoscopic submucosal dissection. Pathology revealed a 54 mm × 43 mm differentiated-type predominant adenocarcinoma with focal undifferentiated-type component that was confined to the mucosa without ulceration. Eleven years after endoscopic submucosal dissection, lymph node metastasis along the lesser curve was incidentally detected on magnetic resonance imaging and diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy. The patient received distal gastrectomy with D2 lymph node dissection. A resected lymph node revealed a well-differentiated adenocarcinoma with a poorly differentiated component; thus, the final diagnosis was late recurrence of early gastric cancer originally treated by endoscopic submucosal dissection. This report demonstrates that metastatic recurrence may occur in curative endoscopic submucosal dissection for early gastric cancer and that gastric cancer can recur even after more than 5 years.

A 55-year-old-man presented with low-grade fever, general fatigue, appetite loss and body weight loss. An electrocardiogram (ECG) showed the presence of long QT syndrome (LQTS), and laboratory test...

We herein report a unique case of type B2 thymoma-associated myasthenia gravis which was ameliorated by immunosuppressive therapy in combination with chemotherapy. However, the patient subsequently developed pure red cell aplasia and marked lymphocytosis after additional chemotherapy aimed at improvement of thymoma. While a separate immunosuppressive regimen was effective for anemia, lymphocytosis was exacerbated. The biopsied thymoma specimen contained CD4+, CD8+, and CD4+/CD8+ T cells, some of which were CD3−, suggesting immature thymocytes. In contrast, majority of the peripheral lymphocytes were polyclonal CD3+/CD8+/T cell receptor (TCR)αβ+ T cells. The CD4/CD8 ratio in the present patient might be affected by immunosuppressive agents, resulting in CD8+ T cell expansion associated with pure red cell aplasia. Although several cases of thymoma accompanied by peripheral T cell lymphocytosis were reported, marked CD8+ T cell proliferation is extremely rare.

Introduction Non-islet cell tumor hypoglycemia is a rare paraneoplastic syndrome associated with tumors. Although it mainly occurs in solid tumors of mesenchymal and epithelial origin, but rarely also in hematopoietic and neuroendocrine origin. Case presentation We describe a 65-year-old man with a muscle-invasive bladder urothelial carcinoma, which rapidly progressed against systemic chemotherapy consisting of gemcitabine and cisplatin. Notably, the patient developed hypoglycemia at the terminal stage of the disease. Pathological diagnosis was giant cell urothelial carcinoma, which was strongly positive for insulin-like growth factor-II in immunohistochemistry. We established patient-derived xenograft from insulin-like growth factor-II producing bladder urothelial carcinoma that caused non-islet cell tumor hypoglycemia. Although we evaluated the efficacy of the neutralizing antibody, there was no statistically significant inhibitory effect on tumor growth. Conclusion To the best of our knowledge, this is the first report of insulin-like growth factor-II-producing urothelial carcinoma that have been recapitulated in a patient-derived xenograft model.

Background/Aims: The aim of the present study was to evaluate the efficacy of magnifying narrow band imaging with acetic acid spray (MA-NBI) in differentiating category 4/5 lesions from category 3 lesions of superficial non-ampullary duodenal epithelial tumors (SNADETs) as per Vienna Classification and to compare the diagnostic performances of both MA-NBI and magnifying narrow band imaging (M-NBI). Methods: We retrospectively identified 60 resected SNADETs (31 category 3 lesions and 29 category 4/5 lesions) in 60 patients who underwent M-NBI and MA-NBI preoperatively. We evaluated vascular and surface patterns using M-NBI and MA-NBI for characterizing category 3 and 4/5 lesions. The surface pattern was classified as tubular, villous, or mix structure using MA-NBI. In addition, lesions with disorganized and unclear structures with irregular margins that can be clearly recognized by MA-NBI were defined as irregular surface structures. Results: For MA-NBI, category 4/5 lesions had a significantly higher mix structure rate and higher irregular surface structure rate than category 3 lesions (62 vs. 16%, p < 0.001, and 86 vs. 19%, p < 0.001, respectively). The diagnostic accuracy of MA-NBI using mix and irregular surface structures for identifying category 4/5 lesions was as follows: sensitivity, 62/86%; specificity, 84/77%; positive predictive value, 78/78%; negative predictive value, 70/86%; and accuracy, 73/82%. The diagnostic accuracy of MA-NBI using irregular surface structure was significantly higher than that of M-NBI (p < 0.05). Conclusion: MA-NBI may be useful in differentiating between category 3 and category 4/5 lesions of SNADETs.

Aldo-keto reductase family 1 member C3 (AKR1C3) is an enzyme in the steroidogenesis pathway, especially in formation of testosterone and dihydrotestosterone, and is believed to have a key role in promoting prostate cancer (PCa) progression, particularly in castration-resistant prostate cancer (CRPC). This study aims to compare the expression level of AKR1C3 between benign prostatic epithelium and cancer cells, and among hormone-naïve prostate cancer (HNPC) and CRPC from the same patients, to understand the role of AKR1C3 in PCa progression. Correlation of AKR1C3 immunohistochemical expression between benign and cancerous epithelia in 134 patient specimens was analyzed. Additionally, correlation between AKR1C3 expression and prostate-specific antigen (PSA) progression-free survival (PFS) after radical prostatectomy was analyzed. Furthermore, we evaluated the consecutive prostate samples derived from 11 patients both in the hormone-naïve and castration-resistant states. AKR1C3 immunostaining of cancer epithelium was significantly stronger than that of the benign epithelia in patients with localized HNPC (p < 0.0001). High AKR1C3 expression was an independent factor of poor PSA PFS (p = 0.032). Moreover, AKR1C3 immunostaining was significantly stronger in CRPC tissues than in HNPC tissues in the same patients (p = 0.0234). Our findings demonstrate that AKR1C3 is crucial in PCa progression.

Insulin-like growth factor 2 is overexpressed in various cancers, and is associated with a poor prognosis. Also, it is known that insulin-like growth factor 2 is an etiology of non-islet cell tumor hypoglycemia. In this report, we describe a case of unexpected hypoglycemia caused by a dedifferentiated liposarcoma producing insulin-like growth factor 2. A large mass in the retroperitoneum was detected in a 61-year-old man who complained of appetite loss. Despite having no history of diabetes mellitus, hypoglycemia suddenly occurred after admission, but oral glucose therapy was ineffective. After total parenteral nutrition, tumor resection was attempted, but failed as a result of rigid adhesion to the surrounding organs. The patient died of the disease 21 days after surgery. Pathological diagnosis at autopsy revealed dedifferentiated liposarcoma, and immunohistochemical staining showed that the tumor excreted insulin-like growth factor 2. The possibility of an insulin-like growth factor 2-producing tumor should be taken into consideration when we encounter a patient with spontaneous hypoglycemia resistant to glucose substitution therapy.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) has been incorporated into the recent international histological classification of renal tumors. However, to date, there are limited studies describing the clinicopathological features of fumarate hydratase (FH)-deficient RCC, including the hereditary (HLRCC) and sporadic forms. Herein, we present a clinicopathological study of seven cases with FH-deficient RCC. The age of patients ranged from 26 to 70 years with mean and median age of 51.7 and 57 years, respectively. The follow-up data of all patients were available. One patient was alive without the disease and five patients were alive with active disease. One patient died of the disease. Family history of RCC, or skin or uterine smooth muscle tumor within second degree of kinship was present in four of seven patients. Metastasis was observed in all tumors. Metastatic sites included bone, lungs, liver, peritoneum, ovaries, tonsils, or lymph nodes. Grossly, the cut surface of the tumor usually showed light brown, brown, or whitish color. Microscopically, the cytoplasm of the tumor cells was predominantly eosinophilic and all tumors displayed various architectural patterns such as papillary, tubular, solid, or microcystic patterns. Furthermore, two tumors demonstrated a tubulocystic pattern. Sarcomatoid change and rhabdoid features were seen in five tumors and two tumors, respectively. Large cytomegaloviral (CMV) inclusion-like eosinophilic nucleoli surrounded by a clear halo were identified in all tumors. All tumors showed negative immunohistochemical reaction for FH protein. False positive results of TFE3 protein were observed in three tumors. Furthermore, a germline mutation of FH gene was identified in one patient with family history of the disease. In conclusion, FH-deficient RCC includes hereditary and sporadic forms. Grossly, this tumor is solitary and occurs unilaterally. Histologically, the tumor is characterized by various patterns such as papillary, tubular, solid, tubulocystic, or microcystic, has eosinophilic cytoplasm and CMV-like high-grade nuclei. FH-deficient RCCs frequently metastasize to other anatomic sites. TFE immunoreactivity may occur in some FH-deficient RCCs, and immunohistochemistry can accurately diagnose these tumors and mutational analysis of FH gene.

Langerhans cell histiocytosis (LCH) with primary involvement of the upper gastrointestinal (GI) tract is rare. We report 2 adult cases of localized LCH in the upper-GI tract, including the second reported adult case of esophageal LCH and review 11 previously reported cases. Case 1 involved the esophagus of a 61-year-old man; histiocytosis was detected when endoscopy was performed for an examination of epigastric pain. Case 2 involved the stomach of a 56-year-old woman wherein the lesion was detected during a follow-up endoscopy after Helicobacter pylori infection. Both biopsy specimens exhibited diffuse proliferation of mononuclear cells with nuclear convolution and a background of eosinophilic infiltrate. The cells were immunohistochemically positive for CD1a and langerin, and BRAF V600E mutation was detected in Case 2. Follow-up endoscopy for both cases revealed that the lesions disappeared without any treatment. It is important to avoid misdiagnosing LCH of the upper-GI tract as a malignant neoplasm.

BCOR-CCNB3 sarcoma is a recently recognized tumor morphologically and clinically simulating Ewing sarcoma. We herein retrospectively collected clinicopathologic data on BCOR-CCNB3 sarcoma in the Kyoto University Hospital over the last 10 years. Three (20%) bone sarcomas were revealed to be diffusely positive for CCNB3 immunohistochemistry among 15 pediatric cases of undifferentiated sarcoma morphologically similar to Ewing sarcoma, while the other cases showed completely negative staining. The three patients with immunohistochemically CCNB3-positive tumors were all male, aged between 11 and 17, and confirmed to have the BCOR-CCNB3 fusion transcript by RT-PCR. Radiologically, all cases had well-demarcated solid masses with bone destruction. Although the tumors were basically small round cell tumors, less monomorphic histological patterns such as short spindle cells, a myxoid matrix, and hemangiopericytoma-like pattern were also observed in both biopsy and resected specimens. Two patients achieved a complete response after chemotherapy for Ewing sarcoma and osteosarcoma, respectively. These results demonstrated that the application of CCNB3 immunostaining was useful for differentiating BCOR-CCNB3 from a group of 'Ewing-like sarcomas' and may contribute to the evaluation of treatment strategies for bone sarcomas.

Chronic expanding hematoma is defined as a structure with central mass of blood and granulation tissue encapsulated with dense fibrous membrane that slowly grows over a month. We report a case of a 67-year-old man with left adrenal chronic expanding hematoma who underwent surgical resection after 7-year surveillance, presenting natural history of an adrenal chronic expanding hematoma.

Pilomyxoid astrocytoma (PMA) is a recently identified type of pilocytic astrocytoma (PA) with shorter progression-free and overall survival, higher rate of recurrence, and higher risk of leptomeningeal spread compared to pilocytic tumors (WHO grade 2 designation). A case is presented here in which intraoperative imprint smears of a pineal region tumor in a 14-year-old girl revealed cytologic monomorphism, elongated cells with bland nuclei embedded in a myxoid background. The tumor cells possessed uniformly round nuclei with a smooth nuclear outline, fine granular chromatin, and small nucleoli. Slender cytoplasmic fibrillary processes and angiocentric arrangement were observed but Rosenthal fibers or eosinophilic granular bodies were absent. A cytologic diagnosis of PMA of the pineal region was suggested by intraoperative smear preparation. Histology and immunohistochemical results confirmed the final diagnosis. This report shows that smear preparation can be trustworthy for the intraoperative diagnosis of PMA, helping to determine the appropriate neurosurgical procedure and therapeutic implications.

Purpose To assess the incidence of difficulty in complete dissection between the right adrenal gland and the liver at the time of laparoscopic surgery for adrenal tumor and to elucidate its cause histopathologically. Patients and methods Thirty-six patients underwent laparoscopic right adrenalectomy between 2004 and 2011 at our institution. Two reviewers independently assessed difficulty in dissection for the 36 nonedited video records of laparoscopic right adrenalectomy in blinded fashion. Twenty-seven records were evaluable for the judgment of difficulty in dissection between the lower surface of the liver and the right adrenal gland. On the other hand, the gross and microscopic relationship between the right adrenal gland and the surface of the liver was investigated in 32 cadavers. Results Incomplete resection of the adrenal gland was found in 11 of 27 (40.7%) patients. Difficulties in dissection because of adhesions between the liver and the adrenal gland were apparently recognized in 5 of 27 (18.5%) patients. Pathologic assessment for cadavers revealed that capsules between these two organs are partially fused in 10 of 32 (31.3%) cases. Histopathologically, intermingling of parenchymal cells (infiltration through the fibrous capsules) was observed in nine (28.1%) cases. Conclusions The tight adhesion between the lower surface of the liver and the adrenal gland because of intermingling of parenchymal cells of both organs is a major cause of incomplete resection of right adrenalectomy. Surgeons have to keep this fact in mind during right adrenalectomy to avoid unnecessary adverse events.

Primary hepatic neuroendocrine carcinoma (NEC) is rare, and its origin, clinical features, diagnosis and treatment have not been clarified. Primary mixed NEC and hepatocellular carcinoma (HCC) is even rarer and is divided into either combined type or collision type. We report a patient with the combined type of mixed NEC and HCC. A 72-year-old male was diagnosed with HCC and underwent hepatectomy because of the presence of two tumors in his liver. Histological examination demonstrated that one of the tumors had both NEC and HCC components. The transitional zone was noted in the immunohistological examination, and the tumor was determined to be the combined type of primary mixed NEC and HCC. This was the first description of an HCC component being found in an NEC-dominant area in a primary mixed NEC and HCC tumor. Three weeks after hepatectomy, an abdominal computed tomography scan showed extensive regional and para-aortic lymphadenopathy, and early relapse was suspected in the patient. The patient died 3 months after the operation despite treatment with combination chemotherapy. This report describes an unfavorable case and summarizes all the primary mixed NEC and HCC tumor cases that have been previously reported.

Primary clear cell carcinoma (CLCC) of the lung is an extremely rare disease and is a subtype of large cell carcinoma, according to the World Health Organization (WHO) classification. A case is presented here in which intraoperative squash smears in a 53-year-old man revealed sheet and small clusters or tumor cells with prominent nucleoli and fine granular chromatin. Abundant translucent cytoplasm with occasional cytoplasmic vacuoles and intracytoplasmic eosinophilic inclusions was also identified. A cytopathologic diagnosis of a CLCC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Nests of slightly acidophilic clear tumor cells with a prominent cellular membrane and an alveolar growth pattern were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK7, and CA19-9 but were negative for Napsin A, CK20, CDX2, TTF-1, alpha-fetoprotein, chromogranin A, synaptophysin, CD10, and CD56. The diagnosis of primary CLCC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical results, and a detailed systemic examination to exclude a possible extrapulmonary origin. We report here the cytopathological features of CLCC of the lung with an emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.

Objective To evaluate the effect of phytotherapeutic agent, Eviprostat, administered after the establishment of nonbacterial prostatitis (NBP) on the stroma-to-epithelium ratio (S/E ratio), inflammatory scores, tissue macrophage infiltration, and cytokines and chemokines levels in prostate tissue and urine. Materials and Methods Ten-month-old male Wistar rats were castrated and exposed to 17-beta-isomer of estradiol for 30 days to induce NBP. Twenty-five NBP rats were divided into 5 groups: (1) NBP (0) rats sacrificed immediately after the establishment of NBP; (2,3) NBP (30)/control (CTL) and NBP (30)/Eviprostat (EVI) rats fed without or with 0.1% Eviprostat under estradiol-free for 30 days, respectively; and (4,5) NBP (60)/CTL and NBP (60)/EVI rats fed without or with 0.1% Eviprostat under estradiol-free for 60 days, respectively. The S/E ratio, inflammatory scores, and the number of macrophage infiltration in the prostate were assessed. Concentrations of cytokines and chemokines in prostatic tissue and urine were measured by enzyme-linked immunosorbent assay. Results The S/E ratio was significantly increased with time until 60 days under estradiol-free condition (P

Purpose: To assess the incidence of difficulty in complete dissection between the right adrenal gland and the liver at the time of laparoscopic surgery for adrenal tumor and to elucidate its cause histopathologically. Patients and Methods: Thirty-six patients underwent laparoscopic right adrenalectomy between 2004 and 2011 at our institution. Two reviewers independently assessed difficulty in dissection for the 36 nonedited video records of laparoscopic right adrenalectomy in blinded fashion. Twenty-seven records were evaluable for the judgment of difficulty in dissection between the lower surface of the liver and the right adrenal gland. On the other hand, the gross and microscopic relationship between the right adrenal gland and the surface of the liver was investigated in 32 cadavers. Results: Incomplete resection of the adrenal gland was found in 11 of 27 (40.7%) patients. Difficulties in dissection because of adhesions between the liver and the adrenal gland were apparently recognized in 5 o...

e16107Background: Identification of altered metabolic pathways in metastatic renal cell carcinoma (RCC) has the potential to aid in the development of diagnosis and targeted therapies. While altera...

Pulmonary mixed squamous cell and glandular papilloma is an extremely rare neoplasm. This is the first cytological report of such a rare neoplasm. A 59-year-old Japanese man was admitted to the hospital complaining of a persistent cough and bloody sputum. A bronchial endoscopic examination revealed an endobronchial polypoid tumor. Upon bronchial brush cytology by Papanicolaou stain, squamous dysplasia showing mild atypia was suspected. The smears showed moderate cellularity with singly scattered cells or loose clusters of cells, consisting of squamous cells and a few columnar cells. Nuclei of the squamous cells showed mild atypia, but there was no nuclear atypia of the columnar cells. Upon intraoperative pathological examination by frozen section, pulmonary mixed squamous cell and glandular papilloma was suspected. Intraoperative imprint cytology by Ultrafast Papanicolaou stain showed a few differences in comparison with bronchial brush cytology, which were thought to be due to differences in obtaining cytological specimens or the steps prior to the staining. The patient underwent a segmentectomy of the left lung. Histopathological diagnosis confirmed a mixed squamous cell and glandular papilloma. The postoperative course has been uneventful for 5 years after surgery. It was thought that cytology was diagnostically inadequate on its own in the present case. However, mixed squamous cell and glandular papilloma must be considered as another type of pulmonary tumor in cytological preparations, especially in a case showing endobronchial papillary growth by bronchoscopy.

In this study, we examine 3CB2 expression, a marker of radial glia, after intracerebral hemorrhage (ICH). Adult male Sprague-Dawley rats received an intracaudate injection of 100 microL autologous whole blood. Animals were sacrificed, and 3CB2 expression was quantified on Western blot. Single and double labeled immunohistochemistry was used to identify which cells express 3CB2. Neurobehavioral examinations (forelimb placing test) were perfomed as an evaluation of function. By Western blot, 3CB2 was strongly expressed at day 3 and expression persisted for at least 1 month. By immunohistochemistry, 3CB2 immunoreactivity was present in large numbers of astrocytes surrounding the hematoma at day 3 after ICH. At 1 month later, 3CB2 immunoreactivity was co-localized with a neuronal marker (TUC-4). Neurobehavioral function in the 1 month after ICH group was significantly improved compared with that of 3 days after ICH. The ICH-induced 3CB2 expression in astrocytes may reflect an early response of these cells to injury, while the delayed expression in neurons might be a part of the adaptative response to injury, perhaps leading to recovery of neurobehavioral function.