EP29 A rare case of marginal zone lymphoma of the breast complicating primary Sjögren’s syndrome

Abstract Case report - Introduction Primary Sjögren’s patients are a higher risk of developing non-Hodgkin lymphoma (NHL) compared with patients with other autoimmune disorders and to the general population. Parotid and submandibular salivary glands are the most frequent localization of MALT lymphomas in pSS. Here we report a case of marginal zone lymphoma of the breast in a patient with long-standing primary Sjögren’s, and we will discuss the clinical and serological predictors for the development of lymphoma. Case report - Case description A 79-year-old female with a 19-year history of primary Sjögren’s syndrome (anti-Ro, anti-La positive) was reviewed in the rheumatology clinic for progressive worsening of sicca symptoms. Her past medical history included recurrent pulmonary emboli, osteoporosis of the spine, asthma, microscopic colitis, Ischemic heart disease and hypothyroidism. She was a non – smoker and consumed minimal alcohol. Her past surgical history included excision of her left salivary gland, 10 years ago. She was undergoing investigation for a new left breast mass for which a biopsy revealed possible involvement by marginal zone lymphoma. A PCR was performed which was equivocal. Subsequently, she developed a right breast lump and an ultrasound scan showed a well-defined 23 x 10 mm oval hyperechoic lesion in the right upper quadrant and a 29 x 9 mm right axillary lymph node. A staging CT chest abdomen and pelvis and bone marrow sample revealed localized disease. Biopsy of breast lump was performed with PCR analysis. This revealed morphological and immunophenotypical appearances most consistent with a low-grade B –Cell lymphoma and favour a marginal zone lymphoma. The patient was reviewed by an oncologist and was treated with 24 Gy radiotherapy in 12 daily fractions and followed up by the advanced practitioner. Case report - Discussion Primary Sjögren’s Syndrome is an autoimmune disease characterised by lymphocytic infiltration of exocrine glands which can manifest in specific organs or as a systemic illness. Patients are at elevated risk of developing lymphoproliferative diseases including non-Hodgkin's lymphoma with a reported prevalence of 5%. On histological analysis, most patients demonstrate low-grade marginal zone B cell lymphoma with approximately 85% occurring in extranodal locations including the parotid and submandibular glands. Some patients may go on to develop high-grade lymphoma. Concerning overall disease activity, it has been recently demonstrated that a stable moderate/high disease activity, calculated either with the EULAR Sjögren’s syndrome disease activity index (ESSDAI) or with the ClinESSDAI, an ESSDAI variant excluding the biological domain, was independently associated with subsequent lymphoma occurrence. Symptomatic cryoglobulinaemic vasculitis (CV) is observed in about 3–4% of pSS patients and has been linked to the development of lymphoma. Other clinical markers of lymphoma such as palpable purpura, low levels of C4, lymphocytopenia, low levels of IgM, elevated levels of β2-microglobulin Malignant proliferation has been reported in the literature and, to the best of our knowledge, only two case reports of a marginal zone lymphoma of the breast complicating primary Sjögren’s syndrome exist. Case report - Key learning points 1/ This case emphasises the need for careful clinical examination in this exceedingly rare entity. 2/ Although parotid and submandibular gland are commonest extranodal site for NHL, other organs such as thyroid, ovaries and breast might be rarely be affected. 3/ Clinicians should be alert if there are some clinical and serological features such as cryoglobulin and persistently low complement which usually predicts the development of lymphoma.

. Sjö gren's syndrome (SS) can be variable in presentation but in most cases is mild . Unlike other autoimmune disorders, in SS there is a lack of standardised criteria for diagnosis and classification . Some features can be non-specific and like features of fibromyalgia and sarcoidosis . In unclear cases, like this, objective markers like serology or histology (labial gland biopsy) may be more helpful . In lymphadenopathy, depending on size and appearance, further investigations require multidisciplinary discussion to check if regular imaging is more appropriate compared to invasive tests. The frequency of imaging and potential radiation exposure needs careful consideration. . In this case the patient is unwilling to undergo further invasive tests like a biopsy and the lymphadenopathy seen on imaging is thought relatively stable and not amendable to sampling. . The ideal duration of follow up and need for ongoing investigations in this patient remains unclear -advice on monitoring and outcome of similar cases may help guide patient management and reduce anxiety EP28 A CASE OF ANCA VASCULITIS PRESENTING WITH SJÖ GREN'S SEROLOGY

Shazeen Ayub and Marian Regan Royal Derby Hospital, Derby, United Kingdom
Case report -Introduction: Sjö gren's is an autoimmune multisystem disorder characterised by xerostomia, keratoconjunctivitis sicca and extra glandular manifestations. The presence of sicca symptoms helps with diagnosis but up to 20% patients do not have these. The prevalence of lung involvement hasbeen reportedup to 9-24% and includes changes such as NSIP and organising pneumonia. We present an interesting patient who had no sicca symptoms but positive immunology to suggest Sjö gren's. Changes in sequential CT chest scans were in keeping with Connective Tissue Disease-Associated Interstitial Lung disease (CTAILD). However, presentation with an acute renal injury resulted in a diagnosis of ANCA positive vasculitis. Case report -Case description: A 64-year-old Indian gentleman with medical background of controlled asthma was referred after 9 months of investigations for gluteal weakness. Initial blood tests included normal CK, ESR, CRP, vitamin B12, HbA1c and TFTs. Rheumatoid factor was low positive (20IU/ml), CCP negative. ANAwas 1:80with positive Ro,negative dsDNA. MRI of thighs was normal -no evidence of myositis. Nerve conduction studies showed no active denervation to suggest inflammatory myopathy and muscle biopsy showed myopathic features only. A CT scan revealed 3 small lung nodules recommending repeat scan. When seen in rheumatology clinic, there was additional bilateral shoulder arthralgia with no reports of sicca symptoms or rashes. A repeat autoimmune screen and CT chest was sent. His ANA was 1:1280 with Ro antibodies; CT showed new ground glass changes (with old nodules). Organising Pneumonia was suggested, and respiratory opinion sought. Extended myositis screen was negative. When seen in respiratory clinic he had new haematuria-ANCA screen showed positive anti-PR3 antibody (23U/ml) with normal UþEs, urine PCR and CRP 8mg/L. Based on these results a renal biopsy was performed-which showed no obvious morphological abnormalities. Thus, a suspected diagnosis of CTAILD with Sjö gren's was made.
In clinic 2 months later, there was new shortness of breath and haemoptysis. Urine dip showed haematoproteinuria and Chest X-ray showed increase in peri-hilar masses. He was admitted urgently-blood tests showed a decline in renal function-urea 26.8mmol/L, Creatinine 838umol/L, CRP of 435mg/L and Haemoglobin 100g/L. Urgent repeat renal biopsy was done and CT thorax showed deterioration with bilateral consolidation and new lung lesions. Urgent Plasma exchange and dialysis (9 cycles) was given. Initial results from renal biopsy showed presence of crescents and he was started on cyclophosphamide. On this kidney function has improved-urea 18.4mmol/L and Creatinine 302umol/L; he remains on oral cyclophosphamide. Case report -Discussion: With ongoing symptoms, an underlying autoimmune cause of his symptoms was felt likely. However inflammatory markers remained normal and so did CK. Despite this MRI and muscle biopsies were performed -which again were normal. The only tests that were positive were immunology (Ro antibodies) and a CT chest (showing initial small lung nodules). These findings pointed toward CTAILD with Sjö gren's being the likely diagnosis.
As new lung nodules were seen, repeat CT scans were done-which showed gradual interstitial changes-the main radiological differential diagnosis was Organising pneumonia. Further investigations were delayed due to patient travel and COVID, but ongoing respiratory advice was sought. Even with changes in CT findings the patient remained stable with normal inflammatory markers. However, the clinical picture changed quite rapidly over a month (despite 2þ years of previous symptoms) with presentation of pulmonary-renal vasculitis. Plasma exchange and dialysis were given. A good response with a positive renal biopsy confirmed the most likely diagnosis was Granulomatosis with Polyangiitis (GPA). This case was interesting-the main complaint was of myopathy with no physical signs. Despite this biopsy were performed (muscle and kidney), which were all normal. The red herring in his case was a normal renal biopsy-steering usin the directionof CTD-AILD instead of GPA.
Case report -Key learning points: In patients with clear symptoms matching their investigations the diagnosis is often obvious. When this is not the case and symptomatology does not match results (i.e. no Sicca symptoms but positive immunology to suggest Sjö gren's) suspicion should remain high. Multidisciplinary working can provide insight, which this case does highlight-with input required from Neurology, Respiratory and Renal medicine. Negative results should be taken in context with patients and their symptoms. Initial renal biopsy in this case was normal-however after a review, further comments were made on the sparsity of glomeruli in the sample. Therefore, tissue obtained for diagnosis should always be questioned and clinical suspicion should remain high. In addition, repeat investigations (6 monthly CT scans) canhelp note any interval change.
Thorough history and examination in follow up of patients can help look out for evolving changes. With the new symptoms of haemoptysis and haematoproteinuria this pointed us to the eventual diagnosis. The road to diagnosis in this case was prolonged with an acute drop in kidney function and pulmonary haemorrhage needing urgent Plasma exchange and dialysis. Thankfully, the patient continues to make agood recovery. A last point to add is although isolated myalgia has been described as a presentation of systemic vasculitis in the literature, those patients have had elevated CK and positive muscle biopsy. Our patient did not have any positive findings with over 2 years of symptoms. Therefore, we feel this case was unique in presentation and has valid learning points as above. Case report -Introduction: Primary Sjö gren's patients are a higher risk of developing non-Hodgkin lymphoma (NHL) compared with patients with other autoimmune disorders and to the generalpopulation. Parotid and submandibular salivary glands are the most frequent localization of MALT lymphomas in pSS. Here we report a case of marginal zone lymphoma of the breast in a patient with long-standing primary Sjö gren's, and we will discuss the clinical and serological predictors for the development of lymphoma. Case report-Casedescription: A79-year-oldfemalewitha19-yearhistory of primary Sjö gren's syndrome (anti-Ro, anti-La positive) was reviewed in the rheumatology clinic for progressive worsening of sicca symptoms. Her past medical history included recurrent pulmonary emboli, osteoporosis of the spine, asthma, microscopic colitis, Ischemic heart disease and hypothyroidism. She was a non -smoker and consumed minimal alcohol. Her past surgical history included excision of her left salivary gland, 10 years ago. She was undergoing investigation for a new left breast mass for which a biopsy revealed possible involvement by marginal zone lymphoma. A PCR was performed which was equivocal. Subsequently, she developed a right breast lump and an ultrasound scan showed a well-defined 23 x 10 mm oval hyperechoic lesion in the right upper quadrant and a 29 x 9 mm right axillary lymph node. A staging CT chest abdomen and pelvis and bone marrow sample revealed localized disease. Biopsy of breast lump was performed with PCR analysis. This revealed morphological and immunophenotypical appearances most consistent with a low-grade B -Cell lymphoma and favour a marginal zone lymphoma. The patient was reviewed by an oncologist and was treated with 24 Gy radiotherapy in 12 daily fractions and followed up by the advanced practitioner.
Case report -Discussion: Primary Sjö gren's Syndrome is an autoimmune disease characterised by lymphocytic infiltration of exocrine glands which can manifest in specific organs or as a systemic illness. Case report -Introduction: Primary Sjö gren's syndrome is a systemic autoimmune disease affecting the exocrine glands, commonly resulting in dryness of mouth and eyes. It can also rarely present with neurological symptoms most commonly peripheral neuropathies. The case highlights a rare case of sensory and motor neuropathy with some features suggestive of Sjö gren's syndrome as an underlying diagnosis. Case report -Case description: A 54-year-old Caucasian lady was transferred from a local hospital for specialist neurology care. She described widespread paraesthesia over two months progressing to lower limb weakness worsening over a two-day period. Her symptoms further progressed to involve her arms and new blurred vision. On further questioning she reported previous severe mouth ulcers, possible genital ulcers and painful jaw swelling with long standing history of dry mouth. On thorough neurological examination, the positive findings were mild ptosis of the right eye, paraesthesia on palpation of face, upper limbs had a flaccid tone with reduced power and pseudoathetosis of outstretched arms, reduced proprioception, and absent reflexes. Lower limbs were more affected with worse power and absent proprioception. Schirmer's test showed normal tear production but saliva production was reduced. MRI brain and spine were reported as pathological enhancement in both optic nerves, no obvious brain parenchymal abnormality, no obvious spinal cord abnormality. Lumbar puncture CSF pro 0.38, white cells 12 (poly 50%, mono 50%), red cells 3700, no organisms on gram stain, opening pressure 21.5 cmH 2 O. Sural nerve biopsy demonstrated profound loss of sensory axons, severe loss of large myelinated fibres in all fascicles with motor nerve involvement. Muscle biopsy demonstrated chronic neurogenic atrophy. Rheumatology screen showed positive anti Ro 52 antibodies (on an extended myositis screen). EMG demonstrated neurophysiological evidence of widespread marked loss of sensory axons in the upper and lower limbs and partial loss of motor axons in several lower limb territories. USS parotid glands showed some possibly mildly abnormal areas, minor salivary gland biopsy was normal. She received methylprednisolone, IV immunoglobulin and two courses of plasma exchange. Given some improvement following this treatment, further immunosuppression was felt to be appropriate. Initially Mycofenolate mofetil was started and Rituximab is now being considered.
Case report -Discussion: This case demonstrates a mixed neuropathy picture. Following thorough investigations, many differential diagnoses of mixed neuropathy were considered and excluded (e.g. Guillain Barre, Syphilis, MS, HIV, Hepatitis). Neurological symptoms can develop before the onset of sicca symptoms in Sjö gren's syndrome. With a positive Anti Ro52, xerostomia and clinical improvement with methylprednisolone and plasmaphereses it seems likely there is an underlying autoimmune diagnosis in this case and despite a normal biopsy she would meet the 2016 ACR/EULAR classificationcriteria forSjö gren's syndrome.
Case report -Key learning points: Sjö gren's syndrome should be considered as a potential underlying cause in patients with a sensory ganglionopathy. Neurological symptoms can develop before the onset of sicca symptoms in Sjö gren's syndrome.

Premila Kadamban and Jobie Evans
Addenbrooke's Hospital, Cambridge, United Kingdom Case report -Introduction: Autoimmune diseases are a group of disorders where the body produces an immune response against its own tissue constituents. The understanding of the immune mechanisms underlying autoimmunity has significantly deepened and broadened recently.
The viral infection is a well-known trigger of autoimmunity and chronic hepatitis is known to cause various auto-immune diseases; organ-specific orsystemic. Self-reactivity is part of the normal regeneration and healing. Auto-reactive T&B cells are kept dormant by the concerted action of a variety of mechanisms.
Hepatitis C can disrupt this by molecular mimicry, by providing adjuvant and even bydirectly affecting B cell function.
Case report -Case description: We report a case of a 77 yr old Caucasian lady from South Africa who presented to Addenbrooke's hospital complaining of general decline, multiple constitutional symptoms, and low-grade fever for nearly 6 weeks. She did not have any infective symptoms. She had a past medical history of Type 1 DM, Hypothyroidism, Sjö gren's syndrome Osteoporosis and chronic hepatitis C infection which was treated 4 years ago. Family history was not significant, and shewas a non-smoker. She was found to be thin with a BMI of 18, pyrexical with atemperature 37-38'c; otherwise, examinationfindings wereunremarkable. Initial investigations revealed high inflammatory markers with an ESR of 99 and CRP of 120. WCC was within the normal range as were her renal and liver function tests. She was thoroughly investigated for Pyrexia of Unknown Origin. Her septic screen including Echocardiogram was negative. There was no detectable serum Para-protein and tumour markers were negative. Her CT scan of the chest abdomen and pelvis, MRI scan of the spineand PETscan were reported tobenormal. TheSerumPro-calcitonin was low. Rheumatology team was enlisted at this point. On further assessment, the patient mentioned of having an ongoing mild generalised headachedescribed as a 'fullness in the head' and mild generalised scalp tenderness. She also had an aching pain in her legs. There was no history of visual symptoms, jaw, or tongue pain. On examination, she had generalised scalp tenderness which was worse over the left temporal artery. She had a temporal artery biopsy which showed typical features of GCA (disruption of IEL and giant cell) Following which she was commenced on steroids to which she had a remarkable response. After a month she was commenced on Tocilizumab with quick wean off steroids in view of her elevatedrisk for fractures.