Higher risk of phaeochromocytoma/paraganglioma (Phaeo‐Pgl) in SDHD than SDHB carriers: an Australian cohort study

Carriers of succinate dehydrogenase (SDHx) mutations are at risk of developing phaeochromocytomas, catecholamine secreting extra‐adrenal paragangliomas and non‐secretory head and neck paragangliomas and require lifelong surveillance. There is no current consensus on the optimal surveillance strategy. This study describes the outcomes of a cohort of 50 SDHx mutation carriers followed at a tertiary Australian hospital using a surveillance protocol involving annual clinical review with plasma/urine metanephrines and biennial magnetic resonance imaging from skull base to pelvis.     

Giant gastrointestinal stromal tumour of rare sarcomatoid epithelioid subtype:Case study and literature review

Gastrointestinal stromal tumours(GISTs) are the most common mesenchymal tumours of the gastrointestinal tract,but they represent less than 3% of all gastrointestinal tract malignancies.This is a detailed case study of a 52-yearold male patient treated for very uncommon histological subtype of gastric GIST with atypical clinical presentation,asymptomatic progress and late diagnosis.The resected tumour,giant in diameters,was confirmed to represent the most rare histopathologic subtype of GISTs- sarcomatoid epithelioid GIST.We report this case and review the literature with a special focus on pathomorphological evaluation,biological aggressiveness and prognostic factors.To our knowledge this is the first report of giant GIST of very uncommon sarcomatoid epithelioid subtype.It is concluded that clinicians should pay attention to the fact that initial diagnosis may be delayed due to mildly asymptomatic and non-specific clinical presentation.Asymptomatic tumours diagnosed at a late stage,which is often the case,can be large on presentation.Prognosis for patients diagnosed with GIST depend on tumour size,mitotic rate,histopathologic subtype and tumour location.That is why early diagnosis and R0 resection,which is usually feasible and safe even in giant gastric sarcomatoid epithelioid subtype of GISTs,are the key factors for further treatment and good prognosis.     

SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma–paraganglioma syndromes

A genetic predisposition for paragangliomas and adrenal or extra‐adrenal phaeochromocytomas was recognized years ago. Beside the well‐known syndromes associated with an increased risk of adrenal phaeochromocytoma, Von Hippel Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1, the study of inherited predisposition to head and neck paragangliomas led to the discovery of the novel ‘paraganglioma–phaeochromocytoma syndrome’ caused by germline mutations in three genes encoding subunits of the succinate dehydrogenase (SDH) enzyme (SDHB, SDHC and SDHD) thus opening an unexpected connection between mitochondrial tumour suppressor genes and neural crest‐derived cancers. Germline mutations in SDH genes are responsible for 6% and 9% of sporadic paragangliomas and phaeochromocytomas, respectively, 29% of paediatric cases, 38% of malignant tumours and more than 80% of familial aggregations of paraganglioma and phaeochromocytoma. The disease is characterized by autosomal dominant inheritance with a peculiar parent‐of‐origin effect for SDHD mutations. Life‐time tumour risk seems higher than 70% with variable clinical manifestantions depending on the mutated gene. In this review we summarize the most recent knowledge about the role of SDH deficiency in tumorigenesis, the spectrum and prevalence of SDH mutations derived from several series of cases, the related clinical manifestantions including rare phenotypes, such as the association of paragangliomas with gastrointestinal stromal tumours and kidney cancers, and the biological hypotheses attempting to explain genotype to phenotype correlation.     

Nephrogenic adenoma of the renal pelvis: A rare case report and review of the literature

Rationale:Nephrogenic adenoma (NA) is a rare benign lesion of the urinary tract, which rarely occurs in the renal pelvis. Only 19 cases have been reported in the literature. However, there is no detailed report on the clinicopathological features of NA of the renal pelvis.Patient concerns:This case report describes a 46-year-old male patient who was admitted to the hospital for one month because of painless gross hematuria with blood clots. He had a history of hyperuricemia and a family history of gastric cancer.Diagnoses:NA of the renal pelvis was diagnosed pathologically and immunohistochemical.Interventions:The patient underwent laparoscopic nephroureterectomy.Outcomes:The patient recovered well after the operation with no discomfort. In addition, we followed up with the patient regularly post-discharge (approximately 20 months). There were no obvious abnormalities in the results of routine urine culture, computed tomography scan of the abdomen, and cystoscopy during the follow-up period, and the symptoms disappeared completely and did not recur.Lessons:NA of the renal pelvis is extremely rare in the clinic, which can be easily misdiagnosed and overtreated. However, for pathological diagnosis of this disease, specific immunohistochemical staining for preoperative biopsy was reported to be significant, which should be considered by the urologists and pathologists.     

Management of metastatic gastrointestinal stromal tumour in the Glivec era: a practical case-based approach

Gastrointestinal stromal tumour is now recognized as a distinct pathological malignancy and has received much attention over the last few years. Despite almost universal resistance to chemotherapy, a novel therapy, Imatinib, which targets the KIT receptor, has changed the natural history of this disease. We have audited the first 26 consecutive patients with gastrointestinal stromal tumour treated over 4 years at a single institution. A practical guide to the management of common toxicities and drug resistance is reported with a review of the published reports. Many of the strategies used are likely to be widely applicable to the use of targeted therapies in other malignancies.     

日本血吸虫中国株琥珀酸脱氢酶铁硫蛋白真核重组体的构建及其免疫小鼠的保护性研究

目的研究日本血吸虫琥珀酸脱氢酶铁硫蛋白(SjSDISP)全长编码基因DNA疫苗诱导小鼠的免疫保护性效果。方法将全长SjSDISP基因克隆到真核表达载体pcDNA3上,构建真核表达质粒pcDNA3-SjSDISP,用重组裸DNA免疫昆明小鼠3次,间隙2W,末次免疫后第二周进行日本血吸虫尾蚴攻击感染,感染后42 d处死小鼠,剖杀冲虫,计算减虫率和减卵率。结果经双酶切、PCR和测序验证,表明真核表达质粒pcDNA3-SjSDISP构建成功。动物免疫保护性实验结果显示:pcDNA3-SjSDISP疫苗组减虫率较低,与对照组相比减虫效果不明显(P>0.05);但在每克肝卵、每克粪卵和每雌子宫内卵方面,与对照组相比差异均具有显著性(P<0.01)。结论日本血吸虫琥珀酸脱氢酶铁硫蛋白DNA疫苗可能主要在抗血吸虫卵胚发育或抗生殖起作用,具有潜在的疫苗研究与开发价值。     

Expression of Leukemia Inhibitory Factor in Human Pituitary Adenomas: A Morphologic and Immunocytochemical Study

Leukemia inhibitory factor (LIF) is a pleiotropic, neuropoietic cytokine found in bovine, murine, and human fetal and adult pituitary cells, mostly in corticotrophs and somatotrophs. In addition, it has been found in a few GH- and ACTH-producing human pituitary adenomas. The aim of our study was to investigate the presence of LIF in various morphologic types of human pituitary adenomas. Ninety-eight operated pituitary adenomas diagnosed by light microscopy and classified by pituitary hormone immunocytochemistry and electron microscopy were studied. Sixty-eight tumors were functioning and included 15 densely granulated (DG) and 10 sparsely granulated (SG) somatotroph (SM) adenomas, 5 lactotroph (LT), 7 mixed SM-LT and 31 corticotroph (CRT) adenomas. The remaining 30 nonfunctioning tumors included 11 gonadotroph (GON) and 19 null cell (NULL) adenomas. For immunocytochemical demonstration of LIF, a specific polyclonal antiserum was applied on formalin-fixed, paraffin-embedded tissues. The immunohistoscore ranging from 1 to 64 grades was determined by multiplying the immunostaining grade (1–4) by the staining intensity grade (1–4), and by the heterogeneity grade (1–4). Ninety adenomas (92%) were variably immunopositive for LIF. LIF was expressed in 77.5% of CRT, 81.8% of GON, 93.3% of DG-SM, and in all SG-SM, LT, SM-LT and NULL adenomas. LT adenomas showed the highest immunostaining grade, followed by SG-SM, GON, NULL, SM-LT, DG-SM, LT and CRT adenomas. GON adenomas showed the highest immunohistoscore, followed by NULL, DG-SM, SM-LT, SG-SM, LT and CRT adenomas. Nonfunctioning tumors showed a significantly higher immunohistoscore compared to functioning adenomas (p < 0.01). We conclude that LIF expression is frequent in all types of functioning and nonfunctioning pituitary adenomas.     

Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations

We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/-: 77% vs 63%), 39% with liver metastases (SDHB +/-: 27% vs 47%), and 32% with lung metastases (SDHB +/-: 37% vs 29%). The most common sites of bone involvement were thoracic spine (80%; SDHB+/-: 83% vs 77%), lumbar spine (78%; SDHB +/-: 78% vs 75%), and pelvic and sacral bones (78%; SDHB +/-: 91% vs 65%, P=0.04). Subjects with SDHB mutation also showed significantly higher involvement of long bones (SDHB +/-: 78% vs 30%, P=0.007) than those without the mutation. The best overall sensitivity in detecting bone metastases demonstrated positron emission tomography (PET) with 6-[(18)F]-fluorodopamine ([(18)F]-FDA; 90%), followed by bone scintigraphy (82%), computed tomography or magnetic resonance imaging (CT/MRI; 78%), 2-[(18)F]-fluoro-2-deoxy-d-glucose ([(18)F]-FDG) PET (76%), and scintigraphy with [(123/131)I]-metaiodobenzylguanidine (71%). In subjects with SDHB mutation, imaging modalities with best sensitivities for detecting bone metastases were CT/MRI (96%), bone scintigraphy (95%), and [(18)F]-FDG PET (92%). In subjects without SDHB mutations, the modality with the best sensitivity for bone metastases was [(18)F]-FDA PET (100%). In conclusion, bone scintigraphy should be used in the staging of patients with malignant pheochromocytoma and paraganglioma, particularly in patients with SDHB mutations. As for PET imaging, [(18)F]-FDG PET is highly recommended in SDHB mutation patients, whereas [(18)F]-FDA PET is recommended in patients without the mutation.     

Liver cell adenoma: A case report and a review of 30 cases reported in Japan

A 38 year old man with a huge liver cell adenoma extending to the pelvis was treated by left lateral lobectomy. The tumour, which was well-encapsulated by fibrous membrane, was 18 × 19 × 6 cm in size and weighed 1500g. Histopathologically, this tumour was composed of well-differentiated liver cell trabeculae and a small number of pseudobiliary ducts, but no Glisson sheaths. For the past 4 years 8 months he has remained asymptomatic. Thirty cases of liver cell adenoma found in Japanese literature are reviewed here and possible pathogenic implications are discussed.     

Pancreatic paraganglioma diagnosed by endoscopic ultrasound-guided fine needle aspiration: A case report and review of literature

BACKGROUNDPancreatic paragangliomas (PPGL) are rare benign neuroendocrine neoplasms but malignancy can occur. PPGL are often misdiagnosed as pancreatic neuroendocrine tumor or pancreatic adenocarcinoma.CASE SUMMARYWe reviewed 47 case reports of PPGL published in PubMed to date. Fifteen patients (15/47) with PPGL underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Only six (6/15) were correctly diagnosed as PPGL. All patients with PPGL underwent surgical resection except three (one patient surgery was aborted because of hypertensive crisis, two patients had metastasis or involvement of major vessels). Our patient remained on close surveillance as she was asymptomatic.CONCLUSIONAccurate preoperative diagnosis of PPGL can be safely achieved by EUS-FNA with immunohistochemistry. Multidisciplinary team approach should be considered to bring the optimal results in the management of PPGL.     

Gastrointestinal stromal tumour of the rectum： Report of a case and review of literature

Gastrointestinal stromal tumour （GIST） is a rare tumour of the gastrointestinal tract which does not generally originate in the rectum. The authors describe a case of a 70-year-old man who underwent an anterior resection of the rectum for a low-risk GIST. The patient was not given adjuvant chemotherapy with imatinib and is still disease-free 30 mo after surgery. The authors conclude that although rectal GIST is extremely uncommon, it should be included in differential diagnosis when a tumour in the rectum is detected. Biopsy of the tumour is essential, since this makes it possible to reach a sure preoperative diagnosis based on the immunohistological features of the CDl17 and CD34. Although complete surgical resection with negative tumour margins is the principal curative procedure for primary and nonmetastatic tumours, further studies are still needed for the determination of the most effective treatment strategy for patients with rectal GIST.     

Intestinal ischaemia associated with carcinoid tumour: A case report with review of the pathogenesis

A case of ischaemic ileal perforation associated with a macroscopically unapparent ileal carcinoid is described. The mesenteric vessels were non-pulsatile at operation but were anatomically patent when examined by the pathologist. The characteristic elastic perivascular sclerosis of mesenteric vessels, which probably caused a functional vascular obstruction, was only discovered after the histological sections were reviewed. The true incidence of this rare condition may be higher than previously suspected because the perivascular sclerosis can easily be overlooked. Awareness of the association between carcinoid tumour and mesenteric ischaemia may lead to early surgery and an improved outcome.     

Malignant extra-gastrointestinal stromal tumor of the pancreas:Report of two cases and review of the literature

Gastrointestinal stromal tumors(GISTs)are mesenchymal tumors that arise from the gastrointestinal tract.In rare cases,these tumors are found in intra-abdominal sites unrelated to the gastrointestinal tract,such as the mesentery,omentum and retroperitoneum.However,pancreatic extra-gastrointestinal stromal tumors are extremely rare,with only 14 previous cases reported.A 61-year-old man with no clinical symptoms had a routine check-up,during which an abdominal mass located in the pancreas tail was detected.Abdominal surgery was performed with resection of the pancreas tail and the spleen,and he was diagnosed with lowrisk GISTs.Another 60-year-old man with no clinical symptoms underwent Computed tomography which revealed a well-demarcated tumor,6 cm in diameter,in the head of the pancreas.He was diagnosed with pancreatic GISTs.Here,we describe two rare cases of pancreatic GISTs and review the cases previously reported in the literature.     

Gastrointestinal tuberculosis in renal transplant recipients: case report and review of the literature

O. Jarrett, S.A. Grim, E. Benedetti, N.M. Clark. Gastrointestinal tuberculosis in renal transplant recipients: case report and review of the literature
Transpl Infect Dis 2011: 13: 52–57. All rights reserved Abstract: Mycobacterium tuberculosis is an important opportunistic pathogen following renal transplantation and is often associated with adverse outcomes. Gastrointestinal tuberculosis (GITB) is an infrequent manifestation of TB but a potentially lethal one. We present a case of a renal allograft recipient with GITB 18 months after transplant and review other published cases to identify the typical presenting symptoms, risk factors, and natural history. Treatment of GITB is also discussed.     

Peripheral primitive neuroectodermal tumour of the liver: a case report and review of the literature

Peripheral primitive neuroectodermal tumour (PNET) is a malignant mesenchymal tumour. Although PNETs can occur in numerous solid organs, it is an extremely rare tumour entity, specially involving the liver.We report a 19-year-old boy with Hepatitis B Virus (HBV) infection who was diagnosed with a primary PNET of the liver.     

Primary omental malignant solitary fibrous tumour,an extremely rare malignancy: A case report and review of the literature

Primary omental malignant solitary fibrous tumour is an extremely rare neoplasm considering its tumour origin and pathologic characteristics. Solitary fibrous tumour (SFT) is a spindle cell neoplasm that was first described in 1931. SFT is diagnosed at immunohistochemical stain including CD34, bcl2, CD99 and STAT6. Though most of SFTs are benign in nature, 5–15% are malignant. The diagnostic criteria of malignant SFTs are high cellularity, high mitotic activity(>4/10HPF), pleomorphism, necrosis and haemorrhage.We present the case of a 57-year-old male patient diagnosed with primary omental malignant SFT. Neither tumour origin nor pathologic diagnosis were possible based on preoperative information. Nevertheless, tumour resection was performed successfully.Several SFT cases involving omentum without malignant potential have been reported. However, primary omental malignant SFTs are extremely rare with only 3 cases reported in the literature.     

Circulating tumour cells in pancreatic cancer: A systematic review and meta-analysis of clinicopathological implications

BackgroundThe detection and quantification of circulating tumour cells (CTCs) in pancreatic cancer (PC) has the potential to provide prognostic information. The aim of this review was to provide an overview of the literature surrounding CTCs in PC.MethodsA systematic literature review on CTCs in PC between 2005–2020 was performed. Data based on peripheral vein samples were used to determine the positivity rate of CTCs, their prognostic significance and their relative numbers compared to portal vein (PV) samples.ResultsThe overall CTC detection rate in forty-four articles was 65% (95%CI: 55–75%). Detection rate for CellSearch was 26% (95%CI: 14–38%), which was lower than for both filtration and microfluidic techniques. In nine studies with >50 patients, overall survival was worse with CTC positivity (HR 1.82; 95%CI: 1.61–2.05). Five of seven studies which described PV CTC collection provided patient-level data. PV CTC yield was 7.7-fold (95%CI 1.35–43.9) that of peripheral blood.ConclusionsCTCs were detected in the peripheral circulation of most patients with PC and may be related to prognosis and disease stage. PV blood contains more CTCs than peripheral blood sampling. This review points to the maturation of techniques of CTC enrichment, and its evidence base for eventual clinical deployment.