Unexpected discovery of 2 cases of hepatocyte nuclear factor 1α-mutated infracentimetic adenomatosis

We present 2 cases of hepatocyte nuclear factor 1α (HNF1α)-mutated adenomatosis, discovered for reasons unrelated to this disease, and identified using immunohistochemical methods. These new tools may further our understanding of the link between adenomas/adenomatosis subtypes and their complications, and their association with other abnormalities.

Hepatic adenomatosis associated with hormone replacement therapy and hemosiderosis:A case report

We have reported a case of hepatic adenomatosis associated with hormone replacement therapy （estrogen and progesterone） and hemosiderosis caused by excessive blood transfusion for the treatment of chronic myeloid leukemia. A 34-year-old woman was found to have several hepatic tumors on a routine medical examination. The general condition was good. Laboratory studies showed iron overload. Abdominal computed tomography and selective hepatic angiography showed several hypervascular tumors in the right lobe of the liver （up to 20 mm in diameter）. Since hepatocellular carcinoma could not be ruled out, subsegmental hepatectomy was performed. Histopathological examination of the surgical specimen showed hepatic adenomatosis with hemosiderosis. Both hormone replacement therapy and iron overload could be the cause of hepatic adenomatosis.

Erosive Adenomatosis of the Nipple Masquerading as Paget’s Disease: A Case Report

Introduction:Erosive adenomatosis of the nipple is a rare benign lesion involving nipple which can be easily misdiagnosed as more ominous entities such as Pagets disease.Case presentation:A 21-year-old woman presented with a 6-year history of breast erythema involving her left nipple with tenderness and mild itching. The nipple appeared rough and thickened with areas of erosion and fissuring. Physical examination of other areas of breast as well as imaging studies including ultrasound and mammography showed no abnormalities. The histological examination reveal adiagnosis of erosive adenomatosis of nipple (EAN). The patient was treated by a simple surgical excision without complications and recurrence during 9-month follow-up.Discussion:In the early stage, it can mimic eczema, but in the later stage, more serious diagnosis such as Pagets disease should be differential. It is diagnosed by histopathological examination. Surgical excision is an optimal choice for treament with or without plastic reconstruction.Conclusion:EAN should be considered in the diagnosis of erythema and erosion lesions involving nipple. The gold standard for diagnosis is histopathological examination. A prompt and correct diagnosis of EAN can avoid both unnecessary over treatment and patients emotional stress.

MUTYH-associated polyposis: Is it time to change upper gastrointestinal surveillance? A single-center case series and a literature overview

BACKGROUND The presence of Spigelman stage(SS)IV duodenal polyposis is considered the most significant risk factor for duodenal cancer in patients with MUTYH-associated polyposis(MAP).However,advanced SS disease is rarely reported in MAP patients,and no clear recommendations on small bowel(SB)surveillance have been proposed in this patient setting.AIM To research more because that case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced benign SS disease and often involve the distal portion of the duodenum.METHODS We describe a series of MAP patients followed up at the Regina Elena National Cancer Institute of Rome(Italy).A literature overview on previously reported SB cancers in MAP is also provided.RESULTS We identified two(6%)SB adenocarcinomas with no previous history of duodenal polyposis.Our observations,supported by literature evidence,suggest that the formula for staging duodenal polyposis and predicting risk factors for distal duodenum and jejunal cancer may need to be adjusted to take this into account rather than focusing solely on the presence or absence of SS IV disease.Core Tip:Case reports of duodenal cancers in MUTYH-associated polyposis suggest that they may develop in the absence of advanced Spigelman stage(SS)benign disease and often involve the distal portion of the duodenum.In our case series,we identified two(6%)small-bowel adenocarcinomas with no previous history of duodenal polyposis.Our observations,supported by literature evidence,suggest that the formula for staging duodenal polyposis and predicting risk factors for distal duodenum and jejunal cancer should be adjusted to take into consideration the presence of SS IV disease,rather than focusing only on this feature.suggestive of invasive adenocarcinoma.

Liver transplantation for benign liver tumors

Benign liver tumors are common lesions that are usually asymptomatic and are often found incidentally due to recent advances in imaging techniques and their widespread use.Although most of these tumors can be managed conservatively or treated by surgical resection,liver transplantation(LT)is the only treatment option in selected patients.LT is usually indicated in patients that present with life-threatening complications,when the lesions are diffuse in the hepatic parenchyma or when malignant transformation cannot be ruled out.However,due to the significant postoperative morbidity of the procedure,scarcity of available donor liver grafts,and the benign course of the disease,the indications for LT are still not standardized.Hepatic adenoma and adenomatosis,hepatic hemangioma,and hepatic epithelioid hemangioendothelioma are among the most common benign liver tumors treated by LT.This article reviews the role of LT in patients with benign liver tumors.The indications for LT and long-term outcomes of LT are presented.

Current guidelines in the surgical management of hereditary colorectal cancers

Incidence of colorectal cancer(CRC)is on rise.While approximately 70%of all CRC cases are sporadic in nature,20%-25%have familial aggregation and only<5%is hereditary in origin.Identification of individuals with hereditary predilection for CRC is critical,as it has an impact on their overall surgical management including surgical timing,approach&technique and determines the role of prophylactic surgery and outcome.This review highlights the concept of hereditary CRC,provides insight into its molecular basis,possibility of its application into clinical practice and emphasizes the current treatment strategies with surgical management,based on the available international guidelines.

A Synonymous Polymorphism of APCDD1 Affects Translation Efficacy and is Associated with Androgenic Alopecia

The APCDDI （adenomatosis polyposis coli down-regulated 1） gene is an inhibitor of the Wnt signaling pathway, and a rare mutation of this gene has been associated with hereditary hypotrichosis simplex. In this study, the authors aimed to investigate whether common APCDD1 gene polymorphisms contribute to the development of androgenic alopecia. Patients （n = 210） with androgenic alopecia and 98 controls were investigated. SNPs （Single nucleotide polymorphisms） in the coding region of the gene were sequenced. A significant difference in genotype distribution was found for the c. 1781C/T, p.L476L SNP （rs3185480） of the APCDD1 gene. This SNP is located in exon 5 and is associated with a 3.5- and a 2.8-fold increase in risk for the development of androgenic alopecia for homozygote （CI 0.933-13.125; nominal regression P = 0.063） and heterozygote （CI 1.086-7.217; nominal regression P = 0.033） carriers, respectively. These data suggest that the rs3185480 polymorphism contributes to the development of androgenic alopecia. Protein expression experiments revealed that the polymorphism is associated with reduced APCDDI protein abundance. This reduction is likely due to altered codon usage for leucine from a preferred codon （CTC） to a rare codon （CTT）, which might influence translation efficiency and, thus, APCDDI protein level.

Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome

Pancreatic neoplasms producing exclusively glucagon associated with glucagon cell hyperplasia of the islets and not related to hereditary endocrine syndromes have been recently described. They represent a novel entity within the panel of non-syndromic disorders associated with hyperglucagonemia. This case report describes a 36-year-old female with a 10 years history of nonspecific abdominal pain. No underlying cause was evident despite extensive diagnostic work-up. More recently she was diagnosed with gall bladder stones. Abdominal ultrasound, computerised tomography and magnetic resonance imaging revealed no pathologic findings apart from cholelithiasis. Endoscopic ultrasound revealed a 5.5 mm pancreatic lesion. Fine needle aspiration showed cells focally expressing chromogranin, suggestive but not diagnostic of a low grade neuroendocrine tumor. Octreo Scan was negative. Serum glucagon was elevated to 66 pmol/L(normal: 0-50 pmol/L). Other gut hormones, chromogranin A and chromogranin B were normal. Cholecystectomy and enucleation of the pancreatic lesion were undertaken. Postoperatively, abdominal symptoms resolved and serum glucagon dropped to 7 pmol/L. Although H and E staining confirmed normal pancreatic tissue, immunohistochemistry was initially thought to be suggestive of alpha cell hyperplasia. A count of glucagon positive cells from 5 islets, compared to 5 islets from 5 normal pancreata indicated that islet size and glucagon cell ratios were increased, however still within the wide range of normal physiological findings. Glucagon receptor gene(GCGR) sequencing revealed a heterozygous deletion,K349_G359del and 4 missense mutations. This case may potentially represent a progenitor stage of glucagon cell adenomatosis with hyperglucagonemia in the absence of glucagonoma syndrome. The identification of novel GCGR mutations suggests that these may represent the underlying cause of this condition.

APCDD1 as a Co-receptor Positively Regulates Wnt5a/c-Jun Non-Canonical Signaling Pathway

Adenomatosis polyposis down-regulated 1(APCDD1) is a transmembrane glycoprotein that negatively regulates Wnt/β-catenin canonical signaling by binding with Wnt ligands and receptors. We analyzed the role of APCDD1 in the Wnt5a/c-Jun non-canonical signaling pathway and demonstrated that APCDD1 can interact in vitro with Wnt5a, a classical ligand, and Ror2, a receptor of non-canonical Wnt signaling. Furthermore, we verified the binding of APCDD1 and Ror2 in primary cells of mouse skin. Moreover, APCDD1 seems to form a complex with Ror2 and Vangl2 in the cell, and complex formation can be improved by adding Wnt5a. In the presence of Wnt5a and Ror2, APCDD1 can induce the phosphorylation of c-Jun, a transcription factor of Wnt5a non-canonical signaling, and its phosphorylation level is a readout of Wnt5 a signaling. Wound-healing assay shows that APCDD1 accelerates polarized cell migration during Wnt5a-induced wound closure. Therefore,it is very likely that APCDD1 regulates Wnt5a/c-Jun non-canonical signaling as co-receptor binding with both Wnt5a and Ror2.