Expanding the spectrum of progressive familial intrahepatic cholestasis: A report of 3 cases.

Objectives: Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders caused by defects in bile secretion or transport usually presenting as cholestasis in pediatric age. Herewith, we describe 3 PFIC cases with diagnostic challenges and highlight the role of genetic analysis.

Methods: The clinical history, laboratory data, liver biopsy, and molecular analysis for each case were reviewed.

Unveiling lipid-rich ("clear cell") pancreatic neuroendocrine tumor: A small series of two cases with literature review.

This study presents two cases of lipid-rich pancreatic neuroendocrine tumors (PanNETs), a rare variant posing significant diagnostic challenges in fine needle aspiration (FNA) cytology and small biopsies. The first case involves an elderly male with a pancreatic tumor, displaying distinct cytoplasmic vacuoles, while the second case is a middle-aged male present with a pancreatic tail mass exhibiting foamy cytoplasm and eccentric nuclei, infiltrating in the stroma. Both cases did not exhibit typical morphologic features of PanNET but demonstrated cytomorphologic features and infiltrative growth patterns that mimicked adenocarcinoma.

Chlorophyll and pheophytin protonated and deprotonated ions: Observation and theory.

Pheophytin a and chlorophyll a have been investigated by electrospray mass spectrometry in the positive and negative modes, in view of the importance of the knowledge of their properties in photosynthesis. Pheophytin and chlorophyll are both observed intensely in the protonated mode, and their main fragmentation route is the loss of their phytyl chain. Pheophytin is observed intact in the negative mode, while under collisions, it is primarily cleaved beyond the phytyl chain and loses the attaching propionate group.

Experimental and theoretical study of resonant core-hole spectroscopies of gas-phase free-base phthalocyanine.

We studied N 1s inner-shell processes of the free base Phthalocyanine molecule, HPc, in the gas-phase. This complex organic molecule contains three different nitrogen sites defined by their covalent bonds. We identify the contribution of each site in ionized, core-shell excited or relaxed electronic states by the use of different theoretical methods.

Integrated Genomic and Clinicopathologic Approach Distinguishes Pancreatic Grade 3 Neuroendocrine Tumor From Neuroendocrine Carcinoma and Identifies a Subset With Molecular Overlap.

Distinguishing grade 3 pancreatic neuroendocrine tumor (G3 PanNET) from neuroendocrine carcinoma (PanNEC) is a known diagnostic challenge, and accurate classification is critical because clinical behavior and therapies differ. Although current recommendations suggest that immunohistochemistry for p53, Rb, ATRX, and DAXX can distinguish most cases, some cases remain difficult to classify using this approach. In this study, we reviewed 47 high-grade neoplasms originally diagnosed as pancreatic neuroendocrine neoplasms.

Hepatocellular neoplasms with loss of liver fatty acid binding protein: Clinicopathologic features and molecular profiling.

HNF1A-inactivated hepatocellular adenomas (H-HCA) show steatosis, no atypia and loss of liver fatty acid binding protein (LFABP). LFABP loss also occurs in hepatocellular carcinoma (HCC). This study examines 68 LFABP-negative tumors: 33 typical H-HCA, 10 atypical hepatocellular neoplasms (AHN), 7 well-differentiated (WD) HCC, 18 moderately or poorly differentiated (MD/PD) HCC.

Consistent characterization of the electronic ground state of iron(II) phthalocyanine from valence and core-shell electron spectroscopy.

We studied the iron(II) phthalocyanine molecule in the gas-phase. It is a complex transition organometallic compound, for which, the characterization of its electronic ground state is still debated more than 50 years after the first published study. Here, we show that to determine its electronic ground state, one needs a large corpus of data sets and a consistent theoretical methodology to simulate them.

Follicular dendritic cell sarcoma of the cervical lymph node diagnosed on fine needle aspiration cytology.

Follicular dendritic cell sarcomas (FDCS) are rare tumours of lymph nodes and extranodal tissues which are grouped with the histiocytic and dendritic cell neoplasms. The diagnosis is usually made after thorough clinical and pathological examination with immunohistochemical analysis. Difficulties persist in diagnosing FDCS on cytological preparations.

Dialogs in the assessment of neonatal cholestatic liver disease.

Neonatal cholestatic liver disease is rarely encountered by pathologists outside of specialized pediatric centers and navigating the long list of potential diseases can be daunting. However, the differential diagnosis can be rapidly narrowed through open conversations between the pathologist and pediatric gastroenterologist. The dialog should ideally begin before obtaining the liver biopsy and continue through the rendering of the final pathologic diagnosis.

Action spectroscopy of spin forbidden states in the gas phase: A powerful probe for large non-luminescent molecules.

Triplet action spectra of two similar copper porphyrins, copper tetraphenylporphyrin (CuTPP) and copper octaethylporphyrin (CuOEP), have been studied in the gas phase at low temperatures in the absence of external perturbations by using a resonant pump and a 193 nm probe, ionizing the ππ orbital localized on the porphyrin cycle. The molecules were prepared by laser desorption in a disk source, then cooled in a helium supersonic expansion, and finally excited in the Q band system (S ← S). This type of experiment allows the spectroscopic characterization of large non-luminescent molecules in the absence of solvent perturbations.

Water binding to Fe hemes studied in a cooled ion trap: characterization of a strong 'weak' ligand.

The interaction of a water molecule with ferric heme-iron protoporphyrin ([PP Fe]) has been investigated in the gas phase in an ion trap and studied theoretically by density functional theory. It is found that the interaction of water with ferric heme leads to a stable [PP-Fe-HO] complex in the intermediate spin state (S = 3/2), in the same state as its unligated [PP-Fe] homologue, without spin crossing during water attachment. Using the Van't Hoff equation, the reaction enthalpy for the formation of a Fe-OH bond has been determined for [PP-Fe-HO] and [PP-Fe-(HO)].

Genomic profiling of well-differentiated hepatocellular neoplasms with diffuse glutamine synthetase staining reveals similar genetics across the adenoma to carcinoma spectrum.

Well-differentiated hepatocellular neoplasms are currently classified in the World Health Organization scheme as hepatocellular adenoma or hepatocellular carcinoma. There is no recognized diagnostic category for atypical cases with borderline features, and we have designated these as atypical hepatocellular neoplasms. Diffuse glutamine synthetase staining is used as a surrogate marker to detect β-catenin activation, a well-recognized high risk feature in hepatocellular tumors.

Immunohistochemical and molecular features of cholangiolocellular carcinoma are similar to well-differentiated intrahepatic cholangiocarcinoma.

Cholangiolocellular carcinoma is characterized by low grade cytologic atypia, and anastomosing cords and glands resembling cholangioles or canals of Hering. Cholangiolocellular carcinoma has been variously regarded as a subtype of intrahepatic cholangiocarcinoma (World Health Organization 2000), combined hepatocellular-cholangiocarcinoma of stem cell subtype (World Health Organization 2010) and a distinct type of primary liver carcinoma. Capture-based next generation sequencing targeting the coding regions of 479 cancer genes and select introns was performed on 17 cases (5 cholangiolocellular carcinomas, 7 intrahepatic cholangiocarcinomas, 5 mixed cholangiolocellular-intrahepatic cholangiocarcinomas) along with immunohistochemistry for CK19, SALL4, CD56, CD117, and EMA.

The dramatic effect of N-methylimidazole on trans axial ligand binding to ferric heme: experiment and theory.

The binding energy of CO, O2 and NO to isolated ferric heme, [FeIIIP]+, was studied in the presence and absence of a σ donor (N-methylimidazole and histidine) as the trans axial ligand. This study combines the experimental determination of binding enthalpies by equilibrium measurements in a low temperature ion trap using the van't Hoff equation and high level DFT calculations. It was found that the presence of N-methylimidazole as the axial ligand on the [FeIIIP]+ porphyrin dramatically weakens the [FeIIIP-ligand]+ bond with an up to sevenfold decrease in binding energy owing to the σ donation by N-methylimidazole to the FeIII(3d) orbitals.

Mycobacterium chimaera Hepatitis: A New Disease Entity.

Mycobacterium chimaera was identified as a species within the Mycobacterium avium complex in 2004. Until recently, it was predominantly seen in immunocompromised patients. In 2015, an outbreak of disseminated M.

The surprisingly high ligation energy of CO to ruthenium porphyrins.

A combined theoretical and experimental approach has been used to investigate the binding energy of a ruthenium metalloporphyrin ligated with CO, ruthenium tetraphenylporphyrin [RuII TPP], in the RuII oxidation degree. Measurements performed with VUV ionization using the DESIRS beamline at Synchrotron SOLEIL led to adiabatic ionization energies of [RuII TPP] and its complex with CO, [RuII TPP-CO], of 6.48 ± 0.

Genomic profile of appendiceal goblet cell carcinoid is distinct compared to appendiceal neuroendocrine tumor and conventional adenocarcinoma.

Goblet cell carcinoid (GCC) is a rare appendiceal tumor with unique morphologic features that shows glandular and neuroendocrine differentiation on immunohistochemistry. An additional component of adenocarcinoma (AC) can be present (GCC-AC). Both GCC and GCC-AC are staged and treated like AC.

Hepatic angiomyolipoma: mutation analysis and immunohistochemical pitfalls in diagnosis.

Aims: Hepatic angiomyolipoma (AML) often shows epithelioid morphology with inconspicuous fat. Epithelioid component can mimic hepatocellular adenoma (HCA) or carcinoma (HCC). The aims of this study were to examine the expression of commonly used markers for HCA or HCC in hepatic AML and highlight pitfalls in diagnosis.

Grading and staging mucinous neoplasms of the appendix: a case series and review of the literature.

The grading and staging of appendiceal mucinous neoplasms is challenging and fraught with terminology problems, but has critical prognostic and therapeutic implications. We utilized a small case series to examine the grading and staging systems of appendiceal mucinous neoplasms and outline the evidence for the new systems proposed in the upcoming 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual. We reviewed 33 cases of appendiceal mucinous neoplasms with available clinical follow-up data, 6 of which were widely disseminated in the peritoneum.

Dioxygen Binding to Protonated Heme in the Gas Phase, an Intermediate Between Ferric and Ferrous Heme.

With a view to characterizing the influence of the electronic structure of the Fe atom on the nature of its bond with dioxygen (O ) in heme compounds, a study of the UV/Vis action spectra and binding energies of heme-O molecules has been undertaken in the gas phase. The binding reaction of protonated ferrous heme [Fe -hemeH] with O has been studied in the gas phase by determining the equilibrium of complexed [Fe -hemeH(O )] with uncomplexed protonated heme in an ion trap at controlled temperatures. The binding energy of O to the Fe atom of protonated ferrous heme was obtained from a van't Hoff plot.

Appendiceal goblet cell carcinoid: common errors in staging and clinical interpretation with a proposal for an improved terminology.

Goblet cell carcinoid (GCC) is staged and treated as adenocarcinoma (AC) and not as neuroendocrine tumor (NET) or neuroendocrine carcinoma. The term carcinoid may lead to incorrect interpretation as NET. The aim of the study was to explore pitfalls in staging and clinical interpretation of GCC and mixed GCC-AC, and propose strategies to avoid common errors.

Autoimmune hepatitis: review of histologic features included in the simplified criteria proposed by the international autoimmune hepatitis group and proposal for new histologic criteria.

Simplified criteria for diagnosis of autoimmune hepatitis are based on autoantibodies, serum immunoglobulin G, histologic features, and negative viral serology. A score of 6 points is necessary for the designation of probable autoimmune hepatitis and 7 points or more for definite autoimmune hepatitis. The presence of three histologic features is required for categorizing a case as typical (2 points): interface hepatitis with portal lymphocytic/lymphoplasmacytic cells extending into lobule, emperipolesis, and rosettes.