Usefulness of preoperative extracranial imaging in radiologically suspicious glioblastoma in the West of Scotland and proposal of an imaging diagnostic pathway.

INTRODUCTION: A computed tomography chest, abdomen and pelvis scan (CT CAP) is probably unnecessary if a glioblastoma is detected on the initial CT brain (CTB) before more radiologically definitive magnetic resonance imaging (MRI). We audited its frequency to develop and improve our diagnostic management pathway. METHODS: Twelve-month retrospective case series from 2018 of patients having an initial CTB suspicious for glioblastoma. We dichotomised patients into two groups: Group 1, tissue proven; and Group 2, non-tissue proven, owing to increased extracranial comorbidity in Group 2, which might influence a medical decision to request a CT CAP despite the radiological diagnosis of a glioblastoma being obvious on an initial CT. We quantified the frequencies of plain and contrast CTBs, CT CAPs and extracranial malignancy. RESULTS: In total, 131 patients had a CTB suspicious for glioblastoma; of these, 72% had a CT CAP and 17% had extracranial malignancy. In Group 1 (n = 84 [mean age 59 years]), 64% had a CT CAP. Plain CTB was undertaken in 24% of patients and contrast CTB in 76%. Extracranial malignancy was present in 8% and 12%. In Group 2 (n = 47 [mean age 73 years]), 85% had a CT CAP. Plain CTB was undertaken in 22% of patients and contrast CTB in 78%. Extracranial malignancy was present in 33% and 23%. Negative CT CAPs were found in ∼88% of CTBs in Group 1 and ∼75% of CTBs in Group 2. CONCLUSIONS: Patients having an initial contrast CTB suggestive of glioblastoma, prior to definitive MRI, who are going to be managed surgically, having no history of extracranial malignancy, do not necessarily need a CT CAP unless MRI is non-diagnostic.

Massive atrial myxoma: surgical treatment for an incidentaloma causing dyspnoea.

A patient presented having a one-week history of recurrent falls and confusion and weight loss over an unspecified period of time. A chest radiograph revealed bilateral pleural effusions and the patient was treated for community acquired pneumonia. His weight loss and suspicion of malignant disease prompted computer tomography to be conducted. This revealed widespread mediastinal and oesophageal adenopathy. An echocardiogram showed a large hyperechoic mobile mass. Coronary angiography showed complete occlusion of the left anterior descending and right coronary arteries. He underwent two-vessel coronary artery bypass grafting and an atriotomy to excise the myxoma. He experienced no operative complications and no neurological deterioration and was discharged home three weeks later in sinus rhythm. Myxomas can duplicate a broad array of cardiorespiratory symptoms and signs and can often escape detection by being picked up as an incidentaloma.

Bilateral Morgagni hernia: operative discovery of appendix lying on superior pulmonary vein.

A patient presented having an acute abdomen on a background of a twelve-month history of worsening asthma. Computed tomography showed giant bilateral intrathoracic hernias extending to both thoracic apices. Our case was unusual as the defect was bilateral and left-sided. Surgical repair revealed each hernia sac measuring >20 cm and to contain the entirety of the small bowel and colon (including retroperitoneal bowel). The appendix was discovered adjacent to right superior pulmonary vein. Both sacs were excised and the defects dissected and transfixed in a single stage operation. In the post-operative stage, he developed a 6.3 cm fluid collection anterior to the right atrium and a left-sided pleural effusion. Morgagni hernias can escape detection and be attributed to other diagnoses courtesy of false localising signs on clinical examination and symptoms in the history.

Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen.

Although biallelic mutations in non-collagen genes account for <10% of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in FKBP10, which encodes the 65 kDa prolyl cis-trans isomerase, FKBP65, in 38 members of 21 families with OI. These include 10 families from the Samoan Islands who share a founder mutation. Of the mutations, three are missense; the remainder either introduce premature termination codons or create frameshifts both of which result in mRNA instability. In four families missense mutations result in loss of most of the protein. The clinical effects of these mutations are short stature, a high incidence of joint contractures at birth and progressive scoliosis and fractures, but there is remarkable variability in phenotype even within families. The loss of the activity of FKBP65 has several effects: type I procollagen secretion is slightly delayed, the stabilization of the intact trimer is incomplete and there is diminished hydroxylation of the telopeptide lysyl residues involved in intermolecular cross-link formation in bone. The phenotype overlaps with that seen with mutations in PLOD2 (Bruck syndrome II), which encodes LH2, the enzyme that hydroxylates the telopeptide lysyl residues. These findings define a set of genes, FKBP10, PLOD2 and SERPINH1, that act during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result.

Peptidyl 3-hydroxyproline binding properties of type I collagen suggest a function in fibril supramolecular assembly.

Proline residues in collagens are extensively hydroxylated post-translationally. A rare form of this modification, (3S,2S)-l-hydroxyproline (3Hyp), remains without a clear function. Disruption of the enzyme complex responsible for prolyl 3-hydroxylation results in severe forms of recessive osteogenesis imperfecta (OI). These OI types exhibit a loss of or reduction in the level of 3-hydroxylation at two proline residues, α1(I) Pro986 and α2(I) Pro707. Whether the resulting brittle bone phenotype is caused by the lack of the 3-hydroxyl addition or by another function of the enzyme complex is unknown. We have speculated that the most efficient mechanism for explaining the chemistry of collagen intermolecular cross-linking is for pairs of collagen molecules in register to be the subunit that assembles into fibrils. In this concept, the exposed hydroxyls from 3Hyp are positioned within mutually interactive binding motifs on adjacent collagen molecules that contribute through hydrogen bonding to the process of fibril supramolecular assembly. Here we report observations on the physical binding properties of 3Hyp in collagen chains from experiments designed to explore the potential for interaction using synthetic collagen-like peptides containing 3Hyp. Evidence of self-association was observed between a synthetic peptide containing 3Hyp and the CB6 domain of the α1(I) chain, which contains the single fully 3-hydroxylated proline. Using collagen from a case of severe recessive OI with a CRTAP defect, in which Pro986 was minimally 3-hydroxylated, such binding was not observed. Further study of the role of 3Hyp in supramolecular assembly is warranted for understanding the evolution of tissue-specific variations in collagen fibril organization.

Type III collagen, a fibril network modifier in articular cartilage.

The collagen framework of hyaline cartilages, including articular cartilage, consists largely of type II collagen that matures from a cross-linked heteropolymeric fibril template of types II, IX, and XI collagens. In the articular cartilages of adult joints, type III collagen makes an appearance in varying amounts superimposed on the original collagen fibril network. In a study to understand better the structural role of type III collagen in cartilage, we find that type III collagen molecules with unprocessed N-propeptides are present in the extracellular matrix of adult human and bovine articular cartilages as covalently cross-linked polymers extensively cross-linked to type II collagen. Cross-link analyses revealed that telopeptides from both N and C termini of type III collagen were linked in the tissue to helical cross-linking sites in type II collagen. Reciprocally, telopeptides from type II collagen were recovered cross-linked to helical sites in type III collagen. Cross-linked peptides were also identified in which a trifunctional pyridinoline linked both an alpha1(II) and an alpha1(III) telopeptide to the alpha1(III) helix. This can only have arisen from a cross-link between three different collagen molecules, types II and III in register staggered by 4D from another type III molecule. Type III collagen is known to be prominent at sites of healing and repair in skin and other tissues. The present findings emphasize the role of type III collagen, which is synthesized in mature articular cartilage, as a covalent modifier that may add cohesion to a weakened, existing collagen type II fibril network as part of a chondrocyte healing response to matrix damage.

Differences in chain usage and cross-linking specificities of cartilage type V/XI collagen isoforms with age and tissue.

Collagen type V/XI is a minor but essential component of collagen fibrils in vertebrates. We here report on age- and tissue-related variations in isoform usage in cartilages. With maturation of articular cartilage, the alpha1(V) chain progressively replaced the alpha2(XI) chain. A mix of the molecular isoforms, alpha1(XI)alpha1(V)alpha3(XI) and alpha1(XI)alpha2(XI)alpha3(XI), best explained this finding. A prominence of alpha1(V) chains is therefore characteristic and a potential biomarker of mature mammalian articular cartilage. Analysis of cross-linked peptides showed that the alpha1(V) chains were primarily cross-linked to alpha1(XI) chains in the tissue and hence an integral component of the V/XI polymer. From nucleus pulposus of the intervertebral disc (in which the bulk collagen monomer is type II as in articular cartilage), type V/XI collagen consisted of a mix of five genetically distinct chains, alpha1(XI), alpha2(XI), alpha3(XI), alpha1(V), and alpha2(V). These presumably were derived from several different molecular isoforms, including alpha1(XI)alpha2(XI)alpha3(XI), (alpha1(XI))(2)alpha2(V), and others. Meniscal fibrocartilage shows yet another V/XI phenotype. The findings support and extend the concept that the clade B subfamily of COL5 and COL11 gene products should be considered members of the same collagen subfamily, from which, in combination with clade A gene products (COL2A1 or COL5A2), a range of molecular isoforms has evolved into tissue-dependent usage. We propose an evolving role for collagen V/XI isoforms as an adaptable polymeric template of fibril macro-architecture.

[Hairy-cell leukemia heralded by severe influenza. Apropos of 2 similar cases]. / Leucémies à tricholeucocytes annoncées par une grippe grave. A propos de deux observations similaires.

Two severe cases of virus A influenza with splenomegaly are reported. An underlying hematological disorder was suspected in both cases but the diagnosis could not be confirmed during the acute infectious episodes. The exact diagnosis was made two years later in the first case and seven years later in the second case. Both patients lead normal lives seven years later. The authors emphasise the similarity between the two cases with severe influenza at a very early stage of the disease when there were no changes in the blood count to explain the immune deficit.

[Lupos erythematosus discovered during the course of a toxicodermia (author's transl)]. / Lupus érythémateux disséminés révélés par une toxidermie.

The authors describes four cases of lupus erythematosus (LE) diagnosed during the course of a medication toxicodermia, which was always acute and variable in its severity (in one case it concerned a Lyell's syndrome). The lupus affection was made evident by the toxicodermia and lupic manifestations may regress spontaneously after recovery from the skin disorder. This emphasizes the value of clinical and biological testing for the presence of LE in severe cases of toxicodermia in women, more particularly immunofluorescent studies of the basal structures in the cutaneous lesions.

[Kaposi's sarcoma simulating a splenolymphatic lymphoma, toxoplasmosis, and terminal cryptococcus infection (author's transl)]. / Maladie de Kaposi simulant un lymphome splénoganglionnaire, toxoplasmose, cryptococcose terminale.

The authors report a case of Kaposi's sarcome (K.S.) characterized by the small degree of cutaneous involvement as opposed to splenic and lymphatic invasion, lymphoplasmocytic infiltration of the bone marrow, and opportunistic infections (toxoplasmosis, and cryptococcosis). The rapid mortal outcome and the anatomoclinical characteristics of the K.S. enable this case to be classified as one of the rare types of malignant K.S. with pseudo-cryptoccosis features.