Gland Biopsy Research Articles

Ebstein-Barr virus- induced dacryoadenitis in a child: An unusual sign of a common disease and review of literature

Lacrimal gland inflammation, known as dacryoadenitis, is an uncommon condition with various etiologies, ranging from infectious to autoimmune diseases. The clinical course can be acute, subacute, or chronic, with involvement on one or both sides. In the course of mononucleosis, a self-limited eyelid edema is often observed, while dacryoadenitis has been rarely reported. We present the case of an 8-year-old girl with bilateral subacute Epstein–Barr virus-induced dacryoadenitis, who underwent orbital magnetic resonance imaging and gland biopsy, and we performed a comprehensive literature review.

Severe asthma as the initial clinical manifestation of IgG4-related disease: a retrospective clinical study

BackgroundRespiratory involvement is common in immunoglobulin G4-related disease (IgG4-RD). However, severe asthma as the initial clinical manifestation of IgG4-RD is rare and might be neglected by respiratory clinicians. We aimed to explore the clinical characteristics and prognoses of patients with immunoglobulin G4-related disease (IgG4-RD) manifesting as severe asthma.MethodsA retrospective analysis of the clinical characteristics and prognoses of patients with severe asthma who were eventually diagnosed with IgG4-RD was performed in the Peking Union Medical College Hospital from 2013 to 2019.ResultsTwelve patients (5males, 7 females) were included. The mean age at enrollment and age of asthma onset were 59.4 ± 10.1 and 53.8 ± 10.4 years, respectively. The mean duration of asthma symptoms was 5.7 ± 2.0 years. In all patients, the proportion (25.1 ± 10.3%) and count (2.0 ± 1.1) × 109/L of eosinophils in peripheral blood increased. Additionally, all patients exhibited elevated total immunoglobulin E [IgE, (1279.3 ± 1257.9) KU/L] and IgG4 (9155.8 ± 9247.6) mg/dL. Bronchial wall thickening (n = 11) and mediastinal/hilar lymphadenopathy (n = 11) were major chest CT manifestations. All were pathologically diagnosed through surgical biopsy; submandibular gland (n = 8), supraclavicular lymph node (n = 2), stomach (n = 1), rashes (n = 1), lacrimal gland (n = 1) and thoracoscopic lung (n = 1) biopsies were performed. Asthma was well controlled by oral glucocorticoids (GCs), but some patients relapsed during tapering (n = 11). The refractory condition was controlled after increasing the dosage of GCs and add-on immunosuppressants.ConclusionsFor patients with middle age-onset severe asthma with elevated eosinophils, total IgE and IgG4 levels and available salivary gland ultrasound imaging, ruling out IgG4-RD is recommended. GCs used in combination with immunosuppressants is recommended to prevent relapse.

Immunoglobulin G4-associated disease in pulmonology

A brief review and description of two clinical cases of an IgG4-related disease are presented, one with lung and salivary glands involvement, the other with lung involve-ment associated with post-COVID changes and diagnosed clinically as a neoplasm. Verification of an IgG4-associat-ed disease, which is c haracterized by stereotypical clinical manifestations that make differential diagnosis difficult, became possible due to the histological and immunohis-tochemical study of biopsy and surgical specimen of the salivary glands and lungs. Diagnostic criteria developed by Japanese authors in 2019 were used. Literature review and own observations made it possible to assume an IgG4-associated disease affecting the lungs and salivary glands a real-life, but rarely diagnosed form of idiopath-ic fibrosis of various organs, primarily pneumofibrosis. In the IgG4-associated disease the main diagnostical meth-ods with high specificity are histological and immunohis-tochemical ones with antibodies to CD138, IgG, IgG4, and morphometry. They allow to detect massive infiltration of tissue with lymphocytes, eosinophils, and plasma cells expressing IgG4, in combination with obliterating phle-bitis

Feeding a Saccharomyces cerevisiae fermentation product improves udder health and immune response to a Streptococcus uberis mastitis challenge in mid-lactation dairy cows

BackgroundWe aimed to characterize the protective effects and the molecular mechanisms of action of a Saccharomyces cerevisiae fermentation product (NTK) in response to a mastitis challenge. Eighteen mid-lactation multiparous Holstein cows (n = 9/group) were fed the control diet (CON) or CON supplemented with 19 g/d NTK for 45 d (phase 1, P1) and then infected in the right rear quarter with 2500 CFU of Streptococcus uberis (phase 2, P2). After 36-h, mammary gland and liver biopsies were collected and antibiotic treatment started until the end of P2 (9 d post challenge). Cows were then followed until day 75 (phase 3, P3). Milk yield (MY) and dry matter intake (DMI) were recorded daily. Milk samples for somatic cell score were collected, and rectal and udder temperature, heart and respiration rate were recorded during the challenge period (P2) together with blood samples for metabolite and immune function analyses. Data were analyzed by phase using the PROC MIXED procedure in SAS. Biopsies were used for transcriptomic analysis via RNA-sequencing, followed by pathway analysis.ResultsDMI and MY were not affected by diet in P1, but an interaction with time was recorded in P2 indicating a better recovery from the challenge in NTK compared with CON. NTK reduced rectal temperature, somatic cell score, and temperature of the infected quarter during the challenge. Transcriptome data supported these findings, as NTK supplementation upregulated mammary genes related to immune cell antibacterial function (e.g., CATHL4, NOS2), epithelial tissue protection (e.g. IL17C), and anti-inflammatory activity (e.g., ATF3, BAG3, IER3, G-CSF, GRO1, ZFAND2A). Pathway analysis indicated upregulation of tumor necrosis factor α, heat shock protein response, and p21 related pathways in the response to mastitis in NTK cows. Other pathways for detoxification and cytoprotection functions along with the tight junction pathway were also upregulated in NTK-fed cows.ConclusionsOverall, results highlighted molecular networks involved in the protective effect of NTK prophylactic supplementation on udder health during a subclinical mastitic event.

PHACE syndrome with parotid hemangiomas: a unique case report

BackgroundPHACE syndrome is a congenital disorder in infants characterized by the presence of large hemangiomas in the cervicofacial region along with congenital anomalies of the cardiovascular system, brain, and eyes. PHACE syndrome is an extremely rare condition, and PHACE syndrome with parotid hemangiomas has never been reported in the medical literature.Case presentationA 3-month-old female infant presented with cervicofacial plaques that later involved the left eyelids. The plaques blanched on application of pressure and were diagnosed to be hemangiomas. MRI and MRA studies of the brain showed extensive vascular malformations, agenesis of the left internal carotid artery, and hemangiomas in the parotid glands. A biopsy of the parotid glands confirmed the parotid hemangiomas. Bilateral cataracts and subclavian artery with an aberrant origin were also found. On the basis of the hemangiomas and the arterial, cardiovascular, and ocular abnormalities, PHACE syndrome was diagnosed. A multi-disciplinary treatment approach was begun, but the infant died 20 days after presentation to the hospital.ConclusionsPHACE syndrome is an extremely rare condition that has only been described three hundred times in medical literature. It is usually associated with extensive structural, arterial, ocular, and cutaneous anomalies. However, PHACE syndrome with parotid hemangiomas has never been reported in the medical literature. Hemangiomas are the main diagnostic feature and the most common lesion of this disease. This strong association between PHACE syndrome and hemangiomas suggests the parotid hemangiomas seen in our case to be a new addition to the broad spectrum of anomalies associated with PHACE syndrome.

The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer.

Controversies and uncertainty persist in prostate cancer grading. To update grading recommendations. Critical review of the literature along with pathology and clinician surveys. Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.

Nephrological disorders and neurological involvement in pediatric primary Sjogren syndrome:a case report and review of literature

BackgroundSjögren syndrome (SS) is a rare disease in pediatrics, and little attention has been paid to the clinical feature in these patients. To date, there are few cases concern about neurological and nephrological disorders in childhood Sjögren syndrome. We describe a case of Sjögren syndrome in a 12-year-old girl who developed neurological disorders and interstitial nephritis and review the literature currently available on this topic.Case presentationA 12-year-old girl was admitted to our hospital for arthritis and glucosuria. She was required to do labial gland and renal biopsy, because the positive for anti-nuclear antibody and anti-Sjögren syndrome B (anti-SSB) antibody. Then the biopsy was performed revealing the lymphocytic infiltrate in the small area and renal tubular interstitial damage,thus the diagnosis of Sjögren syndrome with tubular interstitial damage was made. Three months later, she presented again with headache, fever, nausea, vomiting and was recovered without drug therapy. Based on the patient’s medical history, laboratory and imaging examination, and treatment, we speculate that the disorders of the nervous system were caused by the Sjögren syndrome. The girl has stable renal function and no residual nervous system damage in the next 1.5 years, but she underwent low dose prednisone therapy because of persistent renal glucosuria.ConclusionsNephrological disorders and neurological involvement are rare manifestations of Sjögren syndrome in children, and rarely presented as the initial symptoms. It should be suspected in children presenting with unexplained renal diseases, neurological abnormalities, or unexplained fever. Although there is no guidelines on the diagnosis and treatment of children Sjögren syndrome are currently available, early recognition and the appropriate treatment of renal damage and neurologic involvement would improve prognosis and prevent complications.

Complimentary Diagnostic Tools for Endometrosis in Biopsies of Mares with Clinical Subfertility

Background: Endometrosis is a multifactorial disease and one of the main causes of infertility in mares, its etiology and pathogenesis are not completely understood. It is defined as peri glandular and/or stromal endometrial fibrosis with glandular alterations. Due to the few clinical symptoms, besides anamnesis and fertility data, endometrosis requires histological confirmation. The histo-morphology and immune histochemical characteristics of the endometrium vary among individuals according to the disease progression. The aim of this research was to combine histology with new immune and histochemical tools for a more precise detection of fibrotic changes of mares with endometrosis.Materials, Methods & Results: The endometrium of forty thoroughbred mares aged 5-18 years, that did not become pregnant during the last two breeding seasons in a Chilean commercial equine breeding center were biopsied. Samples were subjected to conventional histopathology with hematoxylin-eosin as well as to specific histological staining using specific techniques such as Alcian blue and Masson Fontana, aimed to ascertain what types of mucopolysaccharides were present in those samples. In order to have a deeper picture of the progression of the pathology, immune histochemical methods for the detection of vimentin, cytokeratin, progesterone receptor and lymphocyte marker CD3 were used. Finally in order to detect fibrillar collagen we used second harmonic generation (SHG) technique with detects fibrillar collagen without staining, due to intrinsic hyperpolarization ability of this type of collagen, which can be detected by atomic force microscopy. As a result of our research samples were categorized according to the scale of Keeney and Doig into categories I, IIa, IIb and III (45, 42, 7.5 and 5% respectively). These samples also were characterized by the methods listed earlier and a result we found specific staining in 15 samples coming from higher endometrial damage using Masson-Fontana, while acid staining indicative of acid mucopolysaccharides were detected in 97% of the samples. At immunostaining, we found cytokeratin and vimentin differentially expressed as a function of the degree of the lesions. Cytokeratin was detected in glands from healthy mares, but it was almost absent as the injury was increased. Vimentin in turn, was detected in 26 samples with different degree of intensity. In nine animals, vimentin expression was anomalous, and the marker was detected in fibrotic foci concentrically surrounding glands in biopsies of grade I and IIA only. Although progesterone receptor was detected, there was no correlation with endometrosis. Finally, the lymphocyte T specific CD3 marker was positive in 100% of cases analyzed in which moderate lymphocytic infiltration was found by hematoxylin-eosin; however no staining could be detected in mares with more advanced endometrosis. By combining immunofluorescence with the detection of second harmonic it was possible to detect in the same sample two proteins and collagen deposition at the same time, this had not been reported earlier for endometrosis and mares.Discussion: Our results suggest that the combination of the different methods mentioned is useful for validation and further characterization of the routine hematoxylin-eosin, and can be used as a complementary tool for the diagnosis. Of value, it was possible to combine immunofluorescence with SHG in a single sample in situ.

CHRONIC GRAFT-VS-HOST DISEASE: A CASE REPORT

This study presents a case report of a 42-year-old black woman who showed up in a clinic of pathology and stomatology because of oral manifestations of chronic graft-vs-host disease (cGVHD) after allogeneic bone marrow transplant. The disease manifestations showed as multiple white plaques and striations on the lips, labial mucosa, ventral surface of the tongue, oropharynx, palate, and buccal mucosa as well as areas of atrophic mucosa, burning mouth, and xerostomia. Based on the clinical findings and the patient's history, the diagnosis was cGVHD, and an incisional biopsy of the minor salivary glands of the inferior lip was performed to dismiss other pathologies. The patient was referred to medical assistance because of her systemic condition.

Feasibility of repeat and bilateral submandibular gland needle biopsies in Parkinson's disease

IntroductionSubmandibular gland (SMG) biopsies detect pathological alpha-synuclein (aSyn) in patients with Parkinson's disease (PD). The objectives of this study were to determine 1) the feasibility of performing a second SMG biopsy in previously biopsied patients, 2) the feasibility of doing bilateral SMG biopsies, 3) laterality of aSyn density, 4) whether aSyn density changes over time. MethodsSeven PD patients (6 males) previously having positive unilateral SMG biopsies underwent bilateral needle biopsies. Staining with a validated antibody to pathologic p-serine 129 aSyn was performed. ResultsMean age at time of second biopsy was 76 years and mean time between biopsies was 4.1 years. Five subjects had sufficient SMG tissue bilaterally and two only unilaterally for a total of 12/14 glands biopsied having sufficient tissue, all 7 subjects having sufficient tissue on at least one side, and all 12 glands being aSyn positive. There was a 4x increase in aSyn density on average in the repeat biopsy, with 5 subjects having an increase, one no change, and one a decrease in density. Side effects were similar to previous reports; mainly bruising, swelling, slight bleeding. ConclusionsThis is the first published study of bilateral transcutaneous needle biopsies of the SMG in living patients with PD which showed better tissue acquisition and a change in aSyn density over time. While further study is needed, there is potential for SMG biopsies to serve as a tissue biomarker for PD disease progression and potentially as a peripheral outcome measure for anti-aSyn treatment.

Labial Biopsy of Minor Salivary Glands: Indications in Clinical Diagnostics

The Labial Biopsy of the Salivary Minor Glands (LMSGB) is a complementary examination frequently performed in oral surgery since 1968 [1].

Genetic profiling in the diagnosis of hereditary prostate cancer: Where do we stand?

Prostate cancer has a heterogeneous genetic profile compared with other tumour entities. Accordingly, there are also various mutations that increase the risk of prostate cancer. Some genetic variants only have a mild impact, whereas other gene mutations (BRCA1 /2; HOXB13) may increase the risk significantly. All in all, a man with a negative family history is unlikely to be a carrier of mutations that are associated with an increased risk of PCa. However, this likelihood increases if the family history is positive for a known mutation or if there are relatives who were affected at an early age. In such cases, genetic counselling and testing should be considered, with a particular focus on BRCA1/2 mutations and HOXB13 mutations. However, genetic profiling has not had the potential to replace PSA testing, mpMRI of the prostate gland and/or prostate biopsies as part of cancer screening or the diagnostic algorithm in the general population. The presence of mutations associated with PCa merely allows patients to undergo screening earlier and in tighter intervals and possibly receive earlier definitive treatment.

Histopathological Correlation with Multi-Parametric MRI: Clinical Implications for Focal Prostate Radiation Therapy Treatment Planning on a Prospective Trial

While the feasibility of MRI-guided focal prostate therapy has recently been demonstrated, significant concern persists regarding the sensitivity of multi-parametric MRI (mpMRI) in revealing the full extent of disease. As a result, the appropriate population for partial gland therapy remains unknown. We conducted tandem prospective pilot trials investigating the correlation of initial sextant biopsies and mpMRI with targeted and comprehensive biopsies, and the resulting radiotherapeutic treatment implications. Patients with diagnostic biopsies revealing focal Gleason 6-7 disease and staging mpMRI (including T2, DWI and DCE sequences) showing a concordant PIRADS 4-5 lesion were eligible. Biopsies were performed using MRI/trans-rectal ultrasound fusion under electromagnetic sensor navigation, targeting the four corners and center of the MRI lesion, in addition to 12 whole-gland confirmatory biopsies. A cohort of six patients underwent confirmatory biopsies to assess reliability of their standard workup, and eight additional patients were considered for focal prostate SBRT on protocol if histopathology was concordant with initial biopsies and mpMRI. Significance of correlation was analyzed using Fisher’s exact test and Pearson’s chi square. Of the 14 patients enrolled, five had Gleason 6 and nine had Gleason 3+4 disease at diagnosis, with a mean PSA of 5.95 ± 1.72 (mean age: 64.3 years). Absolute concordance of histopathology on targeted and repeat whole gland biopsies was demonstrated in 28.6% of patients, 2/6 in the first group and 2/8 on the subsequent therapeutic protocol (Fisher's p = 0.006; Pearson's p = 0.012). One patient was disqualified due to a prohibitively elevated IPSS. Among the 9 broadly discordant cases (69.2%), three had an additional site of Gleason 6 disease, one had a second site of ipsilateral Gleason 3+4, one had contralateral Gleason 4+3, one had diffuse Gleason 7-9 disease and one had high volume Gleason 8 disease within the target lesion. In two cases, the targeted biopsy was negative for malignancy. Three patients (21.4%, Fisher's p = 0.085, Pearson's p = 0.170) were upstaged to a new NCCN risk category (low → intermediate; low → high; intermediate → high), necessitating substantial modifications in treatment recommendations, including androgen deprivation therapy and targeting of the seminal vesicles. Confirmatory targeted and whole-gland biopsies of initially pathologically and radiographically focal prostate adenocarcinoma revealed additional sites of disease in the majority of patients, and a subset were upstaged with clinical and therapeutic implications. These results suggest that focal therapy or dose escalation based on MRI sequencing may benefit from precise histopathologic correlation, which is currently being further investigated in a national cooperative group prospective clinical trial.

Syringomyelia-like syndrome in neuromyelitis optica spectrum disorder complicated with Sjogren\u2019s syndrome: a case report

BackgroundBesides CSF-flow obstruction, syringomyelia is associated with inflammatory spinal cord lesions. However, syringomyelia-like syndrome concomitant with neuromyelitis optica spectrum disorder (NMOSD) and primary Sjogren’s syndrome (pSS) is extremely rare. Here, we would like to report a case of a patient with syringomyelia-like syndrome in NMOSD complicated with Sjogren’s Syndrome.Case presentationA 64-old male Han Chinese, presented with three episodes of acute demyelinating processes in the central nervous system within 5 years. Firstly, he presented with ascending left lower extremity weakness and numbness, and initially progressive loss of vision in the right eye before 5 years, and subsequently in the right eye 2 months later. High dose corticosteroid therapy was prescribed for this attack. Second, he suffered from refractory gastrointestinal symptoms.such as nausea, vomiting, abdominal pain and early satiety. After the second episode, he received long-term azathioprine and prednisone treatment in low dosages. Six months before admission, he developed the lower back pain and numbness in lower limbs, and urinary incontinence. This time, he complained of acute onset of right lower limb paralysis, paresthesia and urinary incontinence. MRI of the spine revealed a syringomyelia extending from the C7 to T4 levels with serum positive anti-aquaporin-4 antibodies (AQP4-Ab) (indirect immunofluorescence on AQP4 transfected cells). he was serologically positive for both anti-Sjögren’s syndrome-related antigen A and B antibodies and there was reduced salivary flow on scintigraphy. Lip salivary gland (LSG) biopsies were graded (grade four lymphocytic infiltration) according to the Chisholm and Mason classification system and by morphometric analysis. And finally, diagnosed as syringomyelia-like syndrome in NMOSD complicated with Sjogren’s syndrome.ConclusionsAlthough extremely rare, This index patient highlights that syringomyelia could be associated with underlying NMOSD and pSS, and autoimmune disorders should be considered in the initial differential diagnosis, This is very helpful for the therapeutic implications and evaluating curative effect.

Histopathological analysis of salivary gland biopsies in Kumasi: An 8 year retrospective study

The salivary gland shows wide spectrum of findings on histological examination when they are removed at surgery. The findings range from normal to malignant. The major salivary glands include parotid, submaxillary and sublingual while the othe rs found in many other locations in the head and neck region constitute the minor salivary glands. A ll cases of salivary gland tissues received at our department of Pathology between the year 2009 and 2 016 were selected for this study. Data regarding histological diagnosis, age, sex and location were abstracted. The slides for the cases were retrieved from our archive and the histological diagnoses wer e revaluated. In cases where the slides were not found, the blocks were retrieved and new sections w ere cut for histological appraisal. The data obtained were uploaded into excel sheet and descrip tive analysis was carried out using SPSS version 23. Results obtained were presented in tables and c harts. 371 cases of salivary gland specimens were received during the 8 year period with M:F ratio of 1:1.22 average 46 cases per year. Most of the case s were from the major salivary glands with the most c ommon site being parotid gland (52%). The histology showed benign 167 cases (45%), primary ma lignant 103 cases (27.8%), inflammatory and tumour-like 86 cases (23.2%) while 4 cases (1.1%) w ere metastatic and 11 cases (2.9%) were normal. In the present study, most of our salivary gland biops ies were salivary gland tumours of which benign tumours are much more common than the malignant one s. Pleomorphic adenoma and non-Hodgkin lymphomas were the most common histologic types for the benign and malignant neoplasms respectively

Oral manifestations and histopathology of minor salivary gland from patients with Sjögren's Syndrome and its diagnosis in a public health system

Objective: to analyze the oral manifestations, sialometry and the histopathology of the minor salivary glands of patients with Sjögren Syndrome (SS) treated in a public health system and diagnosed according to European American Consensus Group (EACG) criteria. Material and Methods: the 32 patients were submitted to Shirmer test, oral cavity exam, unstimulated and stimulated salivary flow measurement and, in some cases, to the serological testing. For certain patients a minor salivary
 gland biopsy was carried out. Results: 10 patients were diagnosed with Sjögren Syndrome (SS), among whom: 40% were diagnosed with primary (pSS) and 60% with secondary Sjögren Syndrome (sSS). All patients diagnosed with this condition complained of xerostomia and xeropthalmia. Besides xerostomia, the most frequent oral manifestations were difficulty in swallowing, dry lips, hyperemic gums and atrophic change in tongue papillae. The average scores of the Schirmer and salivary flow tests were lower in patients with sSS. Conclusion: the oral signs and symptoms are extremely important in the multisystem involvement of the SS, which emphasizes the dental
 surgeon responsibility in managing these patients. The establishment of multidisciplinary diagnostic centers is of utmost importance, as well as the ability to offer more objective exams in the public health system aiming at increasing the accuracy of Sjögren Syndrome diagnosis.

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

A minor salivary gland (SG) biopsy with focal lymphocytic sialadenitis and a focus score of ≥1 is today’s widely accepted pathological finding confirming the SG component of Sjögren’s syndrome (SS). Adipocytes can occupy a large percentage of the SG area although little is known about their significance in SS lesions. This study aimed to characterise adipose tissue infiltration in labial SG biopsies from 27 SS patients and 28 non-SS sicca controls. Biopsies were evaluated by one oral pathologist and assessed for focus score, acinar atrophy, fatty replacement and non-specific chronic inflammation. Moreover, to explore the SG microenvironment, immunohistochemical staining of paraffin-embedded SG tissue was performed using interleukin-6 (IL-6). The fatty replacement was evident in all SS patients possessing autoantibodies (Ro/SSA and/or La/SSB) as well as a positive SG biopsy (focus score ≥1). Additionally, 62% of SS patients having autoantibodies but a negative biopsy showed fatty infiltration (FI) while non-SS controls demonstrated fatty replacement in only 32% of the cases. Overall, the SS group (mean age 53.0 years) had a significantly higher incidence (p value 0.005) of FI than the non-SS controls (mean age 54.8 years). Interestingly, adipocytes were located in IL-6 rich areas, and IL-6 positive adipocytes were detected. As fat deposition seems to be more recurrent in SGs affected by SS, we propose the assessment of adipose tissue replacement as a helpful tool for diagnostic evaluation in SS. Detection of IL-6 positive adipocytes suggests their involvement in immune reactions. Still, functional studies are needed to investigate the SG microenvironment further.

Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome, Two New Cases and Review of the Literature

Case 1: A 25 year-old woman, presented with asthenia; weight loss; severe hypertension and acute unilateral anterior uveitis. She had also proteinuria; hematuria; aciduria; kidney failure and grade I hypertensive retinopathy. Kidney biopsy showed a non caseating granuloma in the interstitial tissue, and tubulointerstitial nephritis (TIN) with granulomatous lesions in the medullary parenchyma. All explorations were negative but QuantiFERON was 10 times normal without koch’s bacillus. No other sites of granulomas. The patient partially responded to corticoid treatment. She replased after untimely stopping corticosteroids. Corticosteroid-sparing was provided by mycophenolate mofetil. Case 2: A 46 year-old patient, with family history of mother who died of CKD, presented with recurrent anterior uveitis, kidney failure, proteinuria, and inflammatory syndrome, research of infectious agents or auto-immunity origin was negative. Renal biopsy showed TIN lesions in subacute stage; biopsy of the salivary glands showed stage III chronic lymphocytic sialadenitis without Sjogren syndrome or sarcoidosis. The patient received corticosteroid treatment. Discussion: The presence of TIN, recurrent anterior uveitis, no notion of drug intake, response to corticosteroids and exclusion of other diagnoses leads to TINU syndrome. Positivity of Quantiferon is explained by the fact that TINU syndrome is associated with high serological markers in the absence of their corresponding diseases, and presence of chronic lymphocytic sialadenitis explained by these immunological disorders without Sjogren syndrome, Both patients remained well without recurrence of uveitis 2 and 6 years later respectively. Conclusion: TINU syndrome is secondary to immunological disorders as evidenced interstitial infiltrate of the renal parenchyma, the inflammatory disease of the uvea and good response to corticosteroid therapy.

The clinical characteristics of patients with IgG4-related disease with infiltration of the labial salivary gland by IgG4-positive cells

Objectives. Mikulicz's disease (MD) is an immunoglobulin (Ig) G4-related disease with systemic symptoms. Submandibular gland (SMG) biopsy is recommended for patients with possible IgG4-related MD for accurate differential diagnosis; however, it is difficult for certain patients to undergo this procedure. In contrast, labial salivary gland (LSG) biopsy is more convenient. Here we present an analysis of patients with IgG4-related MD whose LSG specimens were infiltrated with abundant IgG4-positive plasma cells.Methods. Sixteen patients diagnosed with IgG4-related MD underwent simultaneous SMG and LSG biopsies. We evaluated patients’ serological and 18F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) and grouped them as LSG+ (LSG specimens with > 40% IgG4-positive plasma cells/IgG-positive plasma cells, 11 patients) or LSG− (LSG specimens with < 40% IgG4-positive plasma cells/IgG-positive plasma cells, 6 patients).Results. There were not significant differences in serum IgG and IgG4 levels between the two groups; however, serum concentrations of soluble interleuikin-2 receptor (sIL-2R) were significantly higher in the LSG+ group. All patients with increased 18F-FDG uptake in their parotid glands were a part of the LSG+ group.Conclusions. When a SMG biopsy is not possible, the serum concentration of sIL-2R and 18F-FDG-PET/CT findings may predict whether LSG biopsy will facilitate the diagnosis of IgG4-related MD.

Does tocilizumab contribute to elevation of rheumatoid factor and induction of paradoxical syaloadenitis in rheumatoid arthritis patients?

A 56-year-old woman, treated with tocilizumab (TCZ) for 8months for severe rheumatoid arthritis (RA), was admitted to the hospital due to the swelling and tenderness of parotid glands. The patient was diagnosed with seropositive erosive RA in 1988, and treated with different disease modifying antirheumatic drugs (DMARDs) that were used together with a low dosage of glucocorticoides, followed by biologic therapy with infliximab and adalimumab which also proved to be inefficient. The patient had an excellent initial response on TCZ therapy. After 8months, she was presented with an extreme enlargement of parotid glands. Bacterial, viral, and granulomatous diseases were excluded. A spectrum of autoantibodies including anti-Ro and anti-La showed normal values, expect for slightly elevated anti-cyclic citrullinated peptide (anti-CCP) and extreme elevation of the rheumatoid factor (RF) to 10,100IU/ml. The biopsy of salivary glands was done and histological specimen showed limphoplasmocytic syaloadenitis. Tocilizumab therapy was stopped and the dosage of glucocorticoids and methotrexate (MTX) was raised. After 6weeks, the patient was in better condition with slightly lower levels of RF (9,010IU/ml). We hypothesise that in this patient, TCZ stimulated RF hyper production which can induce a paradoxical secondary syaloadenitis in RA.