Chronic cholecystitis with follicular lymphoid hyperplasia: nomenclature and diagnostic dilemmas

Background: To revisit the nomenclature, prevalence, histogenesis and the diagnostic dilemmas in cases of cholecystitis with lymphoid hyperplasia received in a private laboratory in one-year duration.Methods: A total of 51 cases of cholecystectomy were examined histopathologically to identify and review all the cases with emphasis on cholecystitis with marked lymphoid infiltration.Results: Out of 51 cholecystectomy specimens, some rare entities were observed such as 4 cases (8%) of xanthomatous change, 2 cases (4%) of cholecystitis with follicular lymphoid hyperplasia and a case of hyalinizing cholecystitis.Conclusions: The literature on cholecystitis with marked lymphoid infiltrate (with or without follicle formation) was overlapping and thus confusing. The same has been simplified with review of literature.

059 Teratoma with glycine, NMDA & VGKC antibodies presenting with severe weakness, respiratory failure & corticospinal tract dysfunction

IntroductionGlycine antibodies are associated with progressive encephalomyelitis with rigidity and myoclonus (PERM) but have been rarely reported to cause myasthenic-like symptoms.1 We present a single patient seen at a tertiary neurology centre with fatigable muscle weakness and corticospinal tract dysfunction with positive glycine, VGKC and NMDA receptor antibodies, associated with an ovarian teratoma expressing neural tissue.CaseA 32 year old female presented with fatigable muscle weakness. Physical examination was atypical for a disease of the neuromuscular junction with features of exaggerated reflexes and clonus. The weakness progressed over 1–2 weeks leading to respiratory failure. Investigations including MRI brain, repetitive stimulation and acetylcholine-receptor antibody studies were all within the normal limits. Studies for neuronal antibodies against intracellular targets were negative. Further investigation revealed positive autoantibodies against Glycine receptor, NMDA (N-Methyl-d-aspartate) receptor and VGKC (voltage-gated potassium channel) with an underlying ovarian teratoma. Complete clinical resolution was achieved with teratoma resection and 2 g/kg course of intravenous immunoglobulin. Histopathological examination of the tumour revealed a mature cystic teratoma with dystrophic calcification. The teratoma included skin, adipose tissue, intestinal type mucosa, and neuroglial tissue in which nerve fibres and ganglion cells are present. A lymphoid infiltrate was concentrated in areas of neural tissue within the teratoma.ConclusionMuscle weakness, corticospinal tract dysfunction and respiratory failure have previously been reported in the context of anti-glycine antibodies. This is the first case where anti-glycine, anti-NMDA and anti-VGKC antibodies have been found in the context of an ovarian teratoma. The autoimmune nature of this condition is emphasised by the lymphoid infiltrate around the neural tissue expressed within the teratoma.Reference1. Carvajal-Gonzalez A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, … Vincent A. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain2014;137(Pt 8):2178–2192.

Role of high-throughput sequencing in the diagnosis of cutaneous T-cell lymphoma

AimsSubstantial clinicopathological overlap exists between cutaneous T-cell lymphoma (CTCL) and benign conditions, leading to diagnostic difficulties. We sought to delineate the utility of high-throughput sequencing (HTS) across a spectrum of histological findings in CTCL and reactive mimics.MethodsOne hundred skin biopsies obtained for clinical concern for CTCL were identified, comprising 25 cases each from four histological categories: ‘definitive CTCL’, ‘atypical lymphoid infiltrate, concerning for CTCL’, ‘atypical lymphoid infiltrate, favour reactive’ or ‘reactive lymphoid infiltrate’. T-cell receptor gamma chain gene (TRG) PCR and T-cell receptor beta chain gene HTS were performed on both skin biopsy and concurrently collected peripheral blood; most peripheral blood samples were also analysed by flow cytometry.ResultsHistologically defined CTCL specimens had significantly higher clonality scores and T-cell fractions via HTS than all other groups (all p<0.002 and p<0.03, respectively). HTS was more diagnostically specific than TRG PCR in skin (100% vs 88%), while diagnostic sensitivity (68% vs 72%) and accuracy (84% vs 80%) were similar. TRG PCR and flow cytometry performed on blood were the least diagnostically useful assays. Some identically sized peaks detected by TRG PCR in concurrent skin and peripheral blood specimens were non-identical by HTS analysis.ConclusionsHTS, by assessing both clonality and T-cell fractions in skin biopsies, is a powerful tool to aid in the diagnosis of CTCL. It is more specific than TRG PCR in distinguishing definitive CTCL from reactive and indeterminate histology. Identically sized peaks by TRG PCR, typically interpreted to be clonally related, are not always clonally identical by sequencing.