[Testicular Malignant Sertoli Cell Tumor with Long-Term Survival After Pulmonary Metastasectomy: A Case Report].

A 45-year-old man was referred to our hospital with a complaint of right scrotal discomfort. With a diagnosis of testicular tumor, right orchiectomy was performed. The tumor was histologically diagnosed as malignant Sertoli cell tumor pT1N0M0. A pulmonary nodule appeared, 53 months after the operation, and increased in size there after. Thoracoscopic left upper lobectomy was performed 64 months after the operation, and the pathological diagnosis was metastasis of malignant Sertoli cell tumor. No recurrence has been observed for 94 months after the resection of the metastatic lesion.

Immunohistochemistry of the oncofetal protein IMP3 is helpful in the diagnosis of intravascular large B-cell lymphoma using skin biopsy.

BACKGROUND: The oncofetal protein insulin-like growth factor 2 mRNA binding protein-3 (IMP3) is expressed in various cancers. In this study, we examined the diagnostic utility of IMP3 immunohistochemistry in the context of intravascular large B-cell lymphoma (IVL). METHODS: We obtained 25 skin biopsy (SB) specimens diagnosed as IVL and nine IVL-negative SB specimens from 27 IVL patients. Additionally, 27 negative SB specimens from 26 non-IVL patients were obtained from our pathology archives. We performed IMP3 immunohistochemistry on these 61 SB specimens, considering IMP3 expression in any mononuclear cell as positive. In selected cases, triple immunostaining for IMP3, PAX5, and CD34 was performed to analyze the origin and location of IMP3-positive cells. RESULTS: IMP3 was expressed in most intravascular lymphoma cells in all the 25 SB specimens diagnosed as IVL. Furthermore, our evaluation revealed the presence of intravascular IMP3-positive B-cells in five of the nine negative SB specimens from IVL patients; however, this was not observed in the 27 SB specimens from non-IVL patients. CONCLUSION: IMP3 was expressed in most IVL cells, and IMP3 immunohistochemistry could serve as a sensitive diagnostic aid for detecting IVL cells in SB.

Performance of Idylla™ RAS-BRAF mutation test for formalin-fixed paraffin-embedded tissues of colorectal cancer.

BACKGROUND: The Biocartis Idylla™ platform is a fully automated, real-time PCR-based diagnostic system. The Idylla™ KRAS and NRAS-BRAF Mutation Tests have been developed for the qualitative detection of mutations in KRAS, NRAS and BRAF genes, facilitating the genomic profiling of patients with colorectal cancer. The aim of the present study was to evaluate clinical performances of these tests in Japan. METHODS: The RAS and BRAF mutation statuses of 253 formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissues were analyzed using the Investigational Use Only Idylla™ KRAS Mutation Test and the Idylla™ NRAS-BRAF Mutation Test and an in vitro diagnostics (IVD) kit (MEBGEN RASKET™-B kit). RESULTS: The success rate for obtaining a valid mutational data without retest of the Idylla tests was 97.6% (247/253): 111 KRAS mutations (43.8%), 9 NRAS mutations (3.6%), and 36 BRAF V600E mutations (14.2%) were detected using the Idylla tests. Compared with the MEBGEN RASKET-B results, the positive concordance rate was 97.4%, the negative concordance rate was 95.7%, and the overall concordance rate was 95.3% (κ = 0.919, 95% CI 0.871-0.967). The average turnaround time to Idylla™ KRAS and NRAS-BRAF Mutation Test was 5.6 working days (range: 3-11 days). CONCLUSION: This result demonstrates a high concordance between the Idylla™ KRAS and NRAS-BRAF Mutation Tests and an existing IVD kit. In this manner, the Idylla™ mutation tests were validated for the detection of clinically significant KRAS, NRAS, and BRAF mutations in FFPE samples from colorectal cancer patients.

[Fecal microbiota transplantation for refractory Clostridioides difficile infection with Crohn's disease in an allogeneic bone marrow transplant recipient].

We report a case of a 15-year-old girl who developed refractory Clostridioides difficile infection (CDI) after allogeneic bone marrow transplantation (BMT). She was treated successfully with fecal microbiota transplantation (FMT). The patient who had aplastic anemia underwent allogeneic BMT from an HLA 1-locus-mismatched unrelated donor. Four months later, she developed gastrointestinal graft-versus-host disease (GVHD), and immunosuppressive treatment improved the GVHD. However, she developed CDI 5 months after BMT and experienced recurrence after that. Fifteen months after transplant, CDI relapsed despite discontinuation of immunosuppressive treatment; thus, she underwent FMT. Colonoscopy at the time of FMT revealed round aphthae, mainly in the ileocecum, and colonic biopsy revealed inflammatory cell infiltration and noncaseating epithelioid granuloma, which fulfilled the diagnostic criteria for Crohn's disease. Following FMT for CDI, she was treated with enteric budesonide and intravenous methotrexate for Crohn's disease. These interventions resulted in a marked improvement in both CDI and Crohn's disease. Twenty-eight months after FMT, both CDI and Crohn's disease remained in remission with oral mesalamine monotherapy.

[Port-Site Metastasis of Prostate Cancer after Robot-Assisted Laparoscopic Prostatectomy : A Case Report].

The incidence of port-site metastasis in urologic laparoscopic surgery is low, especially in prostate cancer, with 4 reported cases to date. A 65-year-old man was introduced to our hospital presenting with gross hematuria and dysuria. His prostate-specific antigen (PSA) level was 3.1 ng/ml. He was diagnosed with poorly differentiated adenocarcinoma of the prostate, Gleason 9 (5＋4), cT3aN0M0 with non-invasive urothelial cancer of bladder (pTaN0M0, low grade). Robot-assisted laparoscopic prostatectomy was performed. Histopathological examination revealed adenocarcinoma, Gleason 9 (5＋4), pT3bN0, and surgical margins were positive. Eighteen weeks postoperatively, local recurrence, lymph node metastases, and a port-site metastasis were observed. Androgen deprivation therapy with 4 courses of induction docetaxel chemotherapy achieved a complete response on imaging study, 2 years postoperatively.

Erythrocyte-rich thrombus aspirated from patients with ST-elevation myocardial infarction: association with oxidative stress and its impact on myocardial reperfusion.

AIMS: Recent studies have demonstrated that erythrocytes are a potential component in atheromatous lesions and thrombus formation in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to determine the associations of red blood cell (RBC) component of coronary thrombi with oxidative stress and myocardial reperfusion. METHODS AND RESULTS: Aspirated thrombi from 178 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, RBCs, fibrin, macrophages, and neutrophils [myeloperoxidase (MPO)]. The thrombi were divided into tertiles according to the percentage of glycophorin-A-positive area: low (glycophorin-A-positive area <33%; n = 60), intermediate (<54 to 33%; n = 59), and high group (≥54%; n = 59). We also measured plasma MPO levels on admission. In the thrombi, the number of MPO-positive cells in the high-RBC group was significantly greater than that in the low-RBC group (high, 927 ± 385; intermediate, 765 ± 406; low, 279 ± 220 cells/mm(2); P< 0.0001). Plasma MPO levels were significantly higher in the high-RBC group than that in the low-RBC group [low 43.1 (25.0-71.6); intermediate 71.0 (32.9-111.2); high 74.3 (31.1-126.4)ng/mL; P< 0.005]. Distal embolization occurred more frequently in the high-RBC group (P= 0.0009). Moreover, the signs of impaired myocardial reperfusion, as indicated by incomplete ST-segment resolution (STR) and lower myocardial blush grades (MBG), and progression of left ventricular remodelling at 6 months were frequently observed in the high-RBC group (high vs. low: STR, P= 0.056; MBG, P< 0.01; remodelling, P< 0.01). CONCLUSION: The present study demonstrated that erythrocyte-rich thrombi contain more inflammatory cells and reflect high thrombus burden, leading to impaired myocardial reperfusion in STEMI patients.

Extrapulmonary lymphangioleiomyomatosis in pelvic and paraaortic lymph nodes associated with uterine cancer: a report of 3 cases.

We report 3 cases of extrapulmonary lymphangioleiomyomatosis incidentally found in pelvic and paraaortic lymph nodes in association with uterine cancers. Three women, 47-year-old, 59-year-old, and 71-year-old, respectively, had uterine cancers and underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymph node excision. None of the 3 patients had tuberous sclerosis complex or lymphangioleiomyomatosis in other organs. None had any history of extrinsic hormonal administration. The postoperative pathologic diagnoses were uterine cervical squamous cell carcinoma for the first patient and endometrioid adenocarcinomas for the second and the third patients. Besides these malignant lesions, all 3 patients showed spindle cell proliferation, 2 to 5 mm in size, in 1 to 8 foci of the pelvic and paraaortic lymph nodes. The spindle cells having small polygonal nuclei and inconspicuous nucleoli with palely eosinophilic cytoplasm, reminiscent of immature smooth muscle cells, proliferated in nested and whorling patterns. Neither cellular atypia nor mitotic figures were observed. Immunohistochemically, these spindle cells were positive for α-Smooth Muscle Actin, Desmin, HMB45, Microphthalmia Transcription Factor, Estrogen receptor, and Progesterone receptor. And the network of the vascular-like channels surrounded by these spindle cells was positive for D2-40. From the pathologic and immunohistochemical findings, the spindle cell proliferation in the lymph nodes is best interpreted as lymphangioleiomyomatosis.

Whole brain radiation therapy for primary central nervous system marginal zone lymphoma: a case report.

A standard radiation therapy protocol for primary central nervous system marginal zone lymphoma (CNS-MZL) has not been established. The International Lymphoma Radiation Oncology Group suggested a radiation therapy dose of 30-36 Gy for lesions of well-defined CNS-MZL. We report a case of relatively low-dose whole brain radiation therapy (WBRT) for ill-defined CNS-MZL. A 56-year-old man who presented with sudden left-sided convulsions and impaired consciousness was diagnosed with CNS-MZL. The tumor had an ill-defined lesion, without cerebrospinal fluid involvement. WBRT, consisting of 25.2 Gy in 14 fractions, was administered owing to the difficulty in target delineation for focal radiation therapy. No chemotherapy was administered during the treatment course. After the 36-month follow-up period, the patient maintained complete remission without neurological disorders. This report describes the usefulness of relatively low-dose WBRT for ill-defined CNS-MZL.

Multiple Gastric Carcinomas Associated with Epstein-Barr Virus and Helicobacter pylori: A Thought-Provoking Case.

BACKGROUND Epstein-Barr virus (EBV) and Helicobacter pylori (HP) infections are associated with gastric carcinoma (GC). We present a thought-provoking case of multiple GCs associated with EBV and HP infections. CASE REPORT HP infection was incidentally detected in an asymptomatic 60-year-old man. Upper endoscopy revealed gastric "kissing" ulcers. The lesions were located in the body of the stomach and measured 25 and 27 mm, respectively. They were diagnosed on pathology as moderately differentiated tubular adenocarcinoma. Imaging revealed no enlarged lymph nodes or distant metastatic lesions. Distal gastrectomy with lymphadenectomy was performed and surgical cure was obtained. The multiple GCs were categorized on pathology as infß ly0 v0 pT1b(SM)UL1N0M0H0P0CY0 pStage IA according to the Japanese classification and as T1bN0M0 Stage IA according to the tumor, node, metastasis classification. Pathological examination revealed remarkable lymphocytic infiltration into the stroma, as shown by in situ hybridization of EBV. These lymphocytic infiltrations were observed only at the sites of GC. In the immunohistochemical examination, in situ hybridization of EBV was positive for EBV-encoded small ribonucleic acid. The patient's postoperative course was uneventful. Hence, an unexpected relationship between EBV infection and multiple GCs was suggested by pathology. Quantitative determination of EBV DNA in peripheral blood was normal postoperatively. Adjuvant chemotherapy was not recommended. HP eradication therapy was successful. The patient remained asymptomatic and developed no recurrence or metastasis for 3 years after surgery. CONCLUSIONS This thought-provoking case suggests that coinfection with EBV and HP increases GC occurrence.

Adrenocorticotropic hormone-dependent hypercortisolism caused by pancreatic neuroendocrine carcinoma: A thought-provoking but remorseful case of delayed diagnosis.

INTRODUCTION AND IMPORTANCE: Definitive diagnosis of functioning neuroendocrine neoplasms (NENs) in the pancreas is challenging. Adrenocorticotropic hormone (ACTH) regulates adrenal cortisol production. Ectopic ACTH secretion by functioning NENs may cause hypercortisolism. PRESENTATION OF CASE: A 62-year-old woman who was receiving medications for hypertension and hyperlipidemia was referred to our hospital because of abnormal blood tests. Diabetes mellitus was initially diagnosed. Dynamic computed tomography and endoscopic ultrasound revealed a 35-mm diameter hypovascular tumor in the distal pancreas and multiple liver metastases. Endoscopic ultrasound-guided fine-needle aspiration resulted in a diagnosis of neuroendocrine carcinoma. The patient developed pancreatic leakage progressing to peritonitis, abscess formation, pleural effusion, and ascites after the fine-needle aspiration biopsy. Her clinical condition deteriorated to a septic state, necessitating emergency surgery comprising distal pancreatectomy, intraperitoneal lavage, and drainage. Wound healing was protracted and accompanied by ongoing high white blood cell counts and neutrophilia. She also developed a gastric ulcer postoperatively. Systematic endocrine investigations were performed because hypercortisolism caused by a functioning NEN was suspected. Eventually, a definitive diagnosis of an ACTH-producing NEN in the pancreas was made. Systemic chemotherapy was proposed; however, the patient and her family opted for palliative treatment only. She died 42 days after the initial diagnosis. CLINICAL DISCUSSION: We here present a patient with ACTH-dependent hypercortisolism attributable to a pancreatic NEN who died of progressive cancer after a delay in definitive diagnosis. CONCLUSION: Detailed investigation, including systematic endocrine examination and functional imaging studies, are important for precise diagnosis of, and appropriate treatment for, NENs.

Survival analysis of patients with duodenal gastrointestinal stromal tumors.

GOALS: To evaluate the survival characteristics of patients with duodenal gastrointestinal stromal tumors (GISTs). BACKGROUND: GISTs represent the most common mesenchymal neoplasms. However, duodenal GISTs are relatively rare, and few studies have been performed with a focus on duodenal GISTs. STUDY: We collected the data of 41 GIST patients including 7 duodenal cases. Clinicopathologic findings and recurrence-free survival (RFS) of duodenal GIST patients were analyzed. RESULTS: The proportion of having any symptoms was 86% in duodenum, 32% in stomach, and 56% in other GISTs (P=0.034), and the most common symptoms of duodenal GISTs were melena and anemia. The 2-year RFS rates were 51.4% in duodenal GISTs, 78.4% in stomach GISTs, and 100% in other GISTs, and duodenal GISTs showed poorer RFS than nonduodenal GISTs (hazard ratio, 5.1; log-rank P=0.019). Particularly, in low-risk and intermediate-risk group, the hazard ratio of recurrence was 12.3 (log-rank P=0.010). Multivariate Cox analysis showed symptom (P=0.007), mitotic index (P=0.011), and tumor location (P=0.043) were significant prognostic factors of recurrence. CONCLUSIONS: RFS of duodenal GISTs was worse than nonduodenal GISTs.

Rabies virus dissemination in neural tissues of autopsy cases due to rabies imported into Japan from the Philippines: immunohistochemistry.

Two Japanese men, 65 and 69 years old, developed rabies in Japan around 2-3 months after dog-bite exposure in the Philippines. Laboratory diagnosis of rabies was made following the detection of rabies virus genome on reverse transcription-polymerase chain reaction from saliva, and on immunohistochemistry of a nuchal skin punch biopsy in one case. The patients died 9 and 19 days after clinical onset. At autopsy, no macroscopic changes in the CNS were observed. Histopathology indicated that eosinophilic and cytoplasmic inclusion bodies, Negri bodies, were seen in neuronal cells of the CNS. Inflammatory cell reactions were scarce, and no apoptosis in the CNS was detected. Immunohistochemistry demonstrated that rabies virus nucleoprotein (N) and phosphoprotein (P) were disseminated to all neural tissues and cells in the body with a similar pattern in both cases. Interestingly, there were no differences of localization between N and P antigen in the brain, but the N antigen was located at the peripheral nerve sheaths and the P antigen was localized in axons. These data indicate that rabies virus dissemination in all neural tissues causes disease development and death. Immunohistochemistry for rabies is a powerful tool to understand the pathogenesis of rabies.

Surgical resection combined with CHOP chemotherapy plus rituximab for a patient with advanced mesenteric diffuse large B cell lymphoma.

Herein is described a mesenteric diffuse large B cell lymphoma (DLBCL) case with a bulky mass which had achieved a complete remission by the combination therapy of a surgical resection and the CHOP chemotherapy with rituximab. A 78 year old man was referred to the Rakuwakai-Otowa Hospital due to a left lower abdominal tumor. Abdominal CT and MRI showed a bowel-like mass in the left lower abdominal cavity. Abdominal US revealed lymph node swellings at the paraaortic region. By the gastro-duodenoscopy, DLBCL of non-Hodgkin's lymphoma was proven at the 2nd portion of the duodenum. On laparotomy, a mass of 8x8cm in size was found at the mesenterium of the ileum, which directly invaded the ileum and the sigmoid mesocolon. A partial resection of the ileum and the sigmoid colon was performed. After the operation, it was determined to be Stage IV DLBCL and the chemotherapy based on the R-CHOP regimen was performed. The regimen was repeated to the 6th course. During the chemotherapy, he was confirmed to have achieved a complete remission. The present case is a rare case in which a Stage IV mesenteric DLBCL with extensive bulky masses had a favorable prognosis. Stage IV mesenteric DLBCLs with extensive bulky masses are thought to be the indication for the combination therapy of surgical resection and multiagent chemotherapy with rituximab.

The role of prophylactic bilateral oophorectomy at the time of initial diagnosis of a unilateral ovarian metastasis in cases with colorectal adenocarcinoma.

BACKGROUND/AIMS: In cases with a macroscopic unilateral ovarian metastasis of colorectal adenocarcinoma, a clear therapeutic policy regarding a prophylactic bilateral oophorectomy is lacking. METHODOLOGY: Four cases of ovarian metastases of colorectal adenocarcinoma are presented. RESULTS: Case 1 is a 63-year-old with ascending colon carcinoma, Dukes' C, and right oophorectomy due to metachronous ovarian metastasis. Case 2 is a 28-year-old with transverse colon carcinoma, Dukes' D, and right oophorectomy due to synchronous ovarian metastasis. Case 3 is a 40-year-old with rectal carcinoma, Dukes' B, and right oophorectomy due to metachronous ovarian metastasis. Case 4 is a 32-year-old with rectal carcinoma, Dukes' D, and bilateral oophorectomy due to synchronous and metachronous ovarian metastases. Later, in cases 1 and 3, in which a unilateral ovary was preserved, ovarian metastases to the preserved ovary were found and caused severe clinical symptoms. However, by that time their general condition did not permit any additional laparotomy. CONCLUSIONS: Without other extensive metastases, if demonstrable diseases are found in a unilateral ovary, a prophylactic bilateral oophorectomy is recommended.

Successfully-treated mesenteric non-Hodgkin's lymphoma involving hepatic mass--a case report.

A mesenteric diffuse large B-cell lymphoma which also involves the liver is very rare. We describe herein a mesenteric diffuse large B-cell lymphoma with hepatic involvement successfully treated by the combination of surgical resection and multiagent chemotherapy. A 77-year-old man was referred to our hospital because of a right lower abdominal tumor. Abdominal computed tomography showed a mass in the mesenterium at the ileocoecal region and multiple mass in the liver. Gallium scintigram showed focal hot uptake at the ileocoecal region and multiple areas of increased Gallium uptake in the liver. With the diagnosis of a mesenteric tumor with liver metastases, a laparotomy was performed. By an intraoperative pathological examination, non-Hodgkin's lymphoma was suggested. The mesenteric mass was completely resected, but additional operative procedures were not done to the liver. After the operation, the patient was determined to have Stage IVB diffuse large B-cell lymphoma, and chemotherapy based on the CHOP-like regimen was given. After the 8th course of such chemotherapy, he was confirmed to have achieved a complete remission by abdominal computed tomography and Gallium scintigram.The Stage IV mesenteric diffuse large B-cell lymphoma involving the liver seems to be an indication for combination therapy of surgical resection and multiagent chemotherapy.

Nonfunctioning pancreatic endocrine tumor presenting with hemorrhage from isolated gastric varices.

Hemorrhage from gastric varices due to left-sided portal hypertension is an unusual presentation for pancreatic endocrine tumor. A case of pancreatic endocrine tumor presenting with gastric variceal hemorrhage secondary to left-sided portal hypertension associated with splenic vein occlusion is presented. A 53-year-old man with hemorrhage from isolated gastric varices was referred to our hospital. Laboratory studies revealed normal liver function. Surveys to identify the cause of gastric varices by an abdominal CT, MRCP, and abdominal angiography revealed splenic vein occlusion secondarily attributed to the pancreatic tail tumor and splenomegaly. The pancreatic tumor was suspected to be a resectable endocrine tumor. A distal pancreatectomy, splenectomy, partial resection of the gastric fundus, and limited lymph node dissection were performed. By the histological examination, the diagnosis of nonfunctioning pancreatic endocrine tumor with malignant potential was determined. Three years after the surgery, the patient is doing well and reveals no sign of recurrence. In this case, the unusual presentation for pancreatic endocrine tumors such as a gastric variceal hemorrhage had an advantage that led to early presentation prior to the development of metastases with possible curative surgery.

Isolated right ventricular metastasis of uterine cervical carcinoma.

Isolated direct metastasis of uterine cervical carcinoma to the right ventricular endocardium is very rare. A 68-year-old woman was initially diagnosed as having stage IIIb squamous cell carcinoma of the uterine cervix, and was treated with radiation therapy. After 2 years, she developed heart failure and presented with a mass in the right ventricle. The results of further examinations were consistent with a tumor or a thrombus in the right ventricle. She underwent excision of the mass under cardiopulmonary bypass, and histopathologic examination of the resected tissue revealed metastatic squamous cell carcinoma of the uterine cervix. She was discharged 3 weeks after the operation, and underwent chemotherapy. However, she was readmitted with drug-induced interstitial pneumonia and died 5 months after the surgery. Patients with an intracardiac mass and a history of uterine cervical cancer should be suspected of having a myocardial metastasis until it is proven otherwise.

Distinctive prepubertal vulval fibroma: a hitherto unrecognized mesenchymal tumor of prepubertal girls: analysis of 11 cases.

Eleven cases of a distinctive previously unrecognized mesenchymal tumor that arises in the vulvar region in the prepubertal years are described. The tumors presented in the vulva (8 cases arising from labia majora) of prepubertal girls (range, 4-12 years; median, 8 years). The preoperative diagnoses were labial mass or swelling, not otherwise specified in 3 cases, hemangioma in 2 cases, lipoma in 2 cases, and lymphangioma and Bartholin cyst/lymphedema in 1 case each. The tumors were unilateral, ill defined, located in the submucosa or subcutaneous tissue, and ranged in size from 2.0 to 8.0 cm in maximum dimension. Microscopically, they were poorly marginated, hypocellular neoplasms composed of bland spindle-shaped cells in a variably collagenous to edematous or myxoid stroma, diffusely infiltrating between preexisting normal vascular, adipose, and neural tissues. No cytologic atypia was identified. Mitotic activity was minimal with no abnormal mitotic figures. The tumor cells were immunoreactive for CD34 (8 of 9 cases) but not for smooth muscle actin, desmin, and S-100 protein. Treatment was by local excision. From the follow-up data available for 9 patients, 3 patients showed locally recurrent tumor after 4, 6, and 13 months, respectively, of which the second case showed a second recurrence 18 months after the first excision. The term "prepubertal vulval fibroma" is suggested because it reflects the distinct features of this seemingly unique, previously uncharacterized, site- and age-specific mesenchymal tumor.