Reactive Infiltrate Research Articles

A Novel MAO-B/SSAO Inhibitor Improves Multiple Aspects of Dystrophic Phenotype in mdx Mice.

Duchenne muscular dystrophy (DMD) is one of the most frequent and severe childhood muscle diseases. Its pathophysiology is multifaceted and still incompletely understood, but we and others have previously shown that oxidative stress plays an important role. In particular, we have demonstrated that inhibition of mitochondrial monoamine oxidases could improve some functional and biohumoral markers of the pathology. In the present study we report the use of dystrophic mdx mice to evaluate the efficacy of a dual monoamine oxidase B (MAO-B)/semicarbazide-sensitive amine oxidase (SSAO) inhibitor, PXS-5131, in reducing inflammation and fibrosis and improving muscle function. We found that a one-month treatment starting at three months of age was able to decrease reactive oxygen species (ROS) production, fibrosis, and inflammatory infiltrate in the tibialis anterior (TA) and diaphragm muscles. Importantly, we also observed a marked improvement in the capacity of the gastrocnemius muscle to maintain its force when challenged with eccentric contractions. Upon performing a bulk RNA-seq analysis, PXS-5131 treatment affected the expression of genes involved in inflammatory processes and tissue remodeling. We also studied the effect of prolonged treatment in older dystrophic mice, and found that a three-month administration of PXS-5131 was able to greatly reduce the progression of fibrosis not only in the diaphragm but also in the heart. Taken together, these results suggest that PXS-5131 is an effective inhibitor of fibrosis and inflammation in dystrophic muscles, a finding that could open a new therapeutic avenue for DMD patients.

Fine-Needle Aspiration Biopsy as a Diagnostic Modality for Orbital Adnexal Lymphoma

Introduction: The aim of this study was to evaluate fine-needle aspiration biopsy (FNAB) as a diagnostic tool for lymphoproliferative orbital lesions in light of recent improvements in cytomorphological and immunologic analyses. Method: Retrospective case series including all orbital FNABs with a lymphoproliferative outcome at Karolinska University Hospital, Stockholm, Sweden during the period 2005–2015. Results: Of the 38 patients included, 31 (82%) were conclusively diagnosed as having lymphoma according to the first FNAB. Disease in 20 patients (65%) could be subclassified. The diagnosis in 7 patients (18%) was either inconclusive, suggestive of lymphoma, or reactive lymphatic infiltrate. These 7 patients were re-investigated, and the initial suspected diagnosis of malignant lymphoma was confirmed in four. Two of the remaining 3 patients were initially diagnosed as having non-lymphoproliferative disease; however, this was later changed to a lymphoproliferative diagnosis following reinvestigation, while the results of both reFNAB and incisional biopsy were inconclusive in the third. Conclusion: In the majority of the 38 patients, a definitive diagnosis of lymphoma could be made based on FNAB alone, using cytomorphological and immunological workup, and subclassification was possible in 20 patients (65%). Primary low-grade malignant orbital lymphomas are traditionally treated with low-dose radiotherapy regardless of subtype, and incisional biopsy was not needed to initiate treatment. Our findings suggest that FNAB is a valid first option for the diagnosis of suspected orbital lymphomas due to the minimal risk of complications compared to incisional biopsy, and the fact that it can be performed as an outpatient procedure with no anesthesia.

CTIM-11. MRNA AGGREGATES ELICIT RAPID IMMUNOLOGIC RESPONSE AND PSEUDOPROGRESSION IN GLIOBLASTOMA PATIENTS

Abstract BACKGROUND Glioblastoma immunotherapy trials remain limited by heterogeneity and the immunosuppressive tumor microenvironment (TME). To overcome these challenges, we developed a novel cancer immunotherapy that leverages use of mRNA lamellar aggregates (RNA-LPA) encoding for personalized glioblastoma antigens to simultaneously reprogram the GBM TME while inducing tumor specific immunity in the periphery. METHODS In a Phase I trial (PNOC020) with an embedded acceleration titration design (ATD) for patients with newly-diagnosed MGMT unmethylated glioblastoma, we sought to assess whether intravenous administration of RNA-LPAs encoding for pp65 mRNA (tumor associated antigen) mixed with personalized tumor mRNA (extracted and amplified from patient specific biopsies) could activate peripheral immunity while simultaneously reprogramming the GBM TME. All patients received surgical resection with adjuvant chemoradiation followed by escalating doses of RNA-LPA (0.625-1.5 µg/kg). RESULTS We have treated 3 patients on the ATD and one patient on the expanded Phase I trial. In all patients treated to date, RNA-LPAs elicited a rapid response (within hours) characterized by release of cytokines (IL-12, TNF-α, IFN-α), chemokines (CCL2, CCL4, CXCL9-10), increase in plasmacytoid dendritic cells and recruitment of peripheral blood mononuclear cells. Over time there was expansion of antigen specific T cells; T cell receptor (TCR) sequencing pre- and post-infusion demonstrated changes to the most prevalent clonotypes by ~10-20%. In the first subject treated on the expanded phase I trial, we observed significant immunologic response after the fourth vaccine, including 20-fold increase in IFN-γ inducible protein-10. One month after vaccine administration, there was marked increase in the enhancing areas on MRI, which on biopsy demonstrated no viable tumor cells and only reactive gliosis, necrosis, and lymphocytic infiltrates. CONCLUSION RNA-LPAs elicit rapid immune activation in the periphery and reprogram the GBM TME into a proinflammatory milieu as evidenced by tissue confirmed pseudoprogression.

P166 Parotid benign lymphoepithelial cyst in connective tissue disease: a rare case series and literature review

Abstract Background/Aims Benign lymphoepithelial lesions are swellings of salivary glands caused by a reactive lymphoid infiltrate with follicular hyperplasia, obliterating the acinar glands and causing proliferation and disruption of the ductal epithelium. These have been described in HIV, lymphoma and Sjögren's syndrome. We report a case series with mixed connective tissue disease/Sjögren's syndrome and reviewed the literature with similar presentations in order to highlight this unusual manifestation. Methods Index patient: A 25-year-old lady presented with a history of arthralgia, fatigue and Raynaud's 3 years ago and was diagnosed by rheumatologist to have MCTD with ANA showing U1RNP, Ro positive and histones antibody positive. She was managed with mycophenolate and improved. A year ago she developed parotitis which improved with antibiotics. She recently came to the outpatient department with painful swelling in the parotid region. Blood counts remain normal, ESR 36 mm/hr , CRP 6 mg/dl, ACE level, HIV screening normal. MRI parotid showed bilateral multiple lymphoepitheial cysts in the parotid glands. Opinion was obtained from oncology and the ENT surgeon. No evidence of malignancy was found. In view of this, consensus opinion among rheumatologists was to stop mycophenolate and give 2gm rituximab. We also reviewed 10 cases of benign lymphoepithelial cyst arising in the parotid region in acquired immunodeficiency syndrome negative patients. Cases were from 8 published articles plus the three cases of benign lymphoepithelial cyst in a mixed connective tissue disease/Sjögren's syndrome in AIDS negative patients reported in Table 1. Most of the patients had been treated surgically, however, immune therapy is sufficient. Results: Conclusion Benign lymphoepitheial cysts have been described in patients with sarcoidosis, HIV, cancer and CTD. Our patients had features of MCTD with Sjögren's syndrome and manifested with benign lymphoepithelial cysts in the parotids, which is very unusual. Parotid swelling in connective tissue disease requires evaluation and multidisciplinary input. Benign lymphoepithelial cysts will not require any surgery; once malignancy is excluded, they will require modification of immune therapy. Disclosure N. Palaniappan: None. S. Nallasivan: None.

Lymphoepithelioma-like gastric adenocarcinoma. Descriptive case series.

Lymphoepithelioma-like gastric adenocarcinoma is characterised by a large reactive lymphoplasmacytic infiltrate in the stroma and islets of undifferentiated cells, which express intense and widespread Epstein-Barr virus (EBV). This tumour type has higher survival rates than other gastric cancers, a more proximal location and less lymphatic spread. Our aim is to describe the clinical and pathological characteristics of our series of lymphoepithelioma-like gastric adenocarcinoma. We selected patients who underwent surgery for gastric adenocarcinoma lymphoepithelioma-like variant from 2014 onwards. The results of the following variables were collected: age (years), sex, pre-diagnostic clinical time (months), gastric tumour location, endoscopic biopsy histology, surgical technique, in situ hybridisation for EBER region (Epstein-Barr virus-associated non-coding RNA), microsatellite instability, degree of differentiation, level of resection, tumour size (cm), TNM T value, lymphadenopathy/resected node ratio, overall survival (months) and vital status. Our experience in the lymphoepithelioma-like variant presents as an advanced gastric cancer, possibly related to long-standing prediagnostic symptoms. It behaves as a tumour with expansive local growth with little capacity for lymphatic or metastatic involvement, which could be explained by the prominent intratumoral lymphoid stroma that acts as an antimetastatic barrier.

3D analyses reveal T cells with activated nuclear features in T-cell/histiocyte-rich large B-cell lymphoma

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) can show variable histological growth patterns and present remarkable overlap with T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL). Previous studies suggest that NLPHL histological variants represent progression forms of NLPHL and THRLBCL transformation in aggressive disease. Since molecular studies of both lymphomas are limited due to the low number of tumor cells, the present study aimed to learn if a better understanding of these lymphomas is possible via detailed measurements of nuclear and cell size features in 2D and 3D sections. Whereas no significant differences were visible in 2D analyses, a slightly increased nuclear volume and a significantly enlarged cell size were noted in 3D measurements of the tumor cells of THRLBCL in comparison to typical NLPHL cases. Interestingly, not only was the size of the tumor cells increased in THRLBCL but also the nuclear volume of concomitant T cells in the reactive infiltrate when compared with typical NLPHL. Particularly CD8+ T cells had frequent contacts to tumor cells of THRLBCL. However, the nuclear volume of B cells was comparable in all cases. These results clearly demonstrate that 3D tissue analyses are superior to conventional 2D analyses of histological sections. Furthermore, the results point to a strong activation of T cells in THRLBCL, representing a cytotoxic response against the tumor cells with unclear effectiveness, resulting in enhanced swelling of the tumor cell bodies and limiting proliferative potential. Further molecular studies combining 3D tissue analyses and molecular data will help to gain profound insight into these ill-defined cellular processes.

Flow cytometry assessment of reactive T-cells distinguishes classic Hodgkin lymphoma from benign lymphadenopathy in children.

BackgroundDetection of classic Hodgkin lymphoma (cHL) neoplastic cells using flow cytometric immunophenotyping (FCI) remains limited. We hypothesized that characterization of the reactive infiltrates could assist in diagnosing cHL in children.MethodsFCI using four‐color staining approaches was performed on 156 lymph node specimens with the following histopathologic diagnoses: cHL (25 cases), reactive lymphoid hyperplasia (RLH, 44 cases), and non‐Hodgkin lymphoma (87 cases).ResultsThe overall concordance of FCI data with the histopathologic results of these cases was 81.4%. A reactive expansion of T‐cells with increased expression of CD45RO was present in the reactive infiltrate of cHL (CD45RO/CD3, 67.5%) and Epstein–Barr virus (EBV) infected RLH (62.7%) but not in EBV‐negative RLH (28.0%). The mean fluorescence intensity (MFI) of CD7 was higher for cHL and differed significantly from EBV‐positive RLH (138.5 vs. 63.8). A proposed diagnostic algorithm markedly elevated the overall concordance rate from 81.4% to 97.4%.ConclusionsImmunophenotyping the reactive infiltrate of lymphoid tissue using flow cytometry is a reliable supplement to histopathology for the rapid diagnosis of pediatric cHL.

Cutaneous reactive B-cell lymphoid proliferations.

Cutaneous lymphoid hyperplasia (CLH), also known as cutaneous pseudolymphoma, is a spectrum of benign conditions characterized by reactive B- and T-cell cutaneous lymphocytic infiltrates. B-cell lymphoid proliferations are a heterogenous group of non-neoplastic cutaneous diseases that must be histopathologically distinguished from cutaneous B-cell lymphomas. These proliferations can be observed as reactive phenomena to infections, medications, allergens, neoplasms, and more. Furthermore, there are many inflammatory conditions that present with reactive B-cell infiltrates, including actinic prurigo, Zoon balanitis, Rosai-Dorfman disease, and cutaneous plasmacytosis. This review summarizes multiple cutaneous B-cell lymphoid proliferations within the major categories of reactive and disease-associated CLH. Further we discuss major discriminating features of atypical CLH and malignancy. Understanding the specific patterns of B-cell CLH is essential for the proper diagnosis and treatment of patients presenting with such lesions.

PD-L1 positive lympho-epithelial lesions in inflammatory prostate.

Ductal epithelial changes (lympho-epithelial lesions-LEL) in prostatic chronic inflammation (CI) are not well studied so far. to investigate LEL immediately adjacent to prostatic CI. We studied LEL in 144 prostatic surgical and autopsy specimens in various types of prostatic CI: NIH-category IV prostatitis (histologic prostatitis-HP), nonspecific granulomatous prostatitis (NSGP), and the reactive lymphoid infiltrates in the vicinity of benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCa). CI is scored as low and high grade (LG, HG) according to the severity of inflammation. LEL was identified in all types of prostatic specimens and in all types of prostatic CI: in 70.9% of patients with HP; in 100% of cases with NSGP; in 68.7% and in 80% adjacent to BPH and PCa respectively. Statistical analysis showed a significant correlation of the presence of LEL with HG CI (p<0.001). LEL showed strong membranous PD-L1 expression. The study presents the first attempt to examine LEL in inflammatory human prostate. PD-L1 positive LEL have no diagnostic organ specificity, although they are a constant histological finding in HG prostatic CI. LEL, inducible after birth by CI, are an integral part of prostate-associated lymphoid tissue (PALT) and of the inflammatory prostatic microenvironment.

Ileitis in Adult Multisystem Inflammatory Syndrome: A Case Report

Multisystem inflammatory syndrome (MIS) can manifest with nonspecific gastrointestinal symptoms, fever, shock, and cardiovascular dysfunction. Compared with children, MIS in adults (MIS-A) is rare. We present a definitive case of MIS-A (based on the Brighton criteria) in a young adult with fever, erythematous rash, and prominent gastrointestinal (ileitis) features, elevated inflammatory markers with evidence of cardiac involvement, and renal injury 4 weeks after confirmed SARS-CoV-2 infection. We highlight the histopathologic features from an ileal biopsy, which demonstrated reactive lymphocytic infiltrates. To our knowledge, this is the first report describing intestinal histopathologic findings in MIS-A.

Expression pattern and diagnostic utility of BCL11B in mature T- and NK-cell neoplasms

BCL11B is an essential transcription factor for T-cell lineage commitment and differentiation, and its dysregulation has been shown to be associated with T-cell tumourigenesis. In this study, we investigated BCL11B expression by immunohistochemical analysis in 120 cases of mature T-cell lymphoma, 34 B-cell lymphomas, 11 NK-cell neoplasms and 17 reactive cutaneous conditions. All cases of mycosis fungoides (n=23), primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (n=8) and T-prolymphocytic leukaemia (n=6) were positive for BCL11B and the staining intensity was higher than that of reactive T-cells. Fourteen of 15 (93%) cases of angioimmunoblastic T-cell lymphoma, 10 of 12 (83%) T-large granular lymphocytic leukaemia and 14 of 20 (70%) peripheral T-cell lymphoma, not otherwise specified, were also positive for BCL11B with an intensity comparable to reactive T-cells. Other T-cell neoplasms were uncommonly positive including one of three (33%) cases of primary cutaneous gamma delta T-cell lymphoma, one of four (25%) cases of subcutaneous panniculitis-like T-cell lymphoma, one of four (25%) cases of hepatosplenic T-cell lymphoma, and one of 20 (5%) cases of anaplastic large cell lymphoma (8 ALK-positive, 12 ALK-negative). T-cells in reactive cutaneous infiltrates were also positive for BCL11B, but staining intensity was much weaker than in mycosis fungoides. All NK-cell (n=11) and B-cell neoplasms (n=34) were negative for BCL11B. In conclusion, BCL11B shows a distinct expression pattern in various T-cell neoplasms. BCL11B appears to have utility as another T-cell marker and may be useful in the differential diagnosis of lymphoid neoplasms.

Lymphoepithelial carcinoma of the maxillary sinus: A case report

Lymphoepithelioma-like carcinoma or lymphoepithelial carcinoma (LEC) of the maxillary sinus is an extremely rare malignancy. It is a rare type of undifferentiated carcinoma, consisting of atypical epithelial cells surrounded by reactive lymphoplasmacytic infiltrate. The paper reports the case of a 76-year-old male patient, with complain of swelling on the hard palate and epistaxis. Biopsy from the hard palate mass showed features consistent with LEC, with contrast-enhanced computed tomography nasopharynx and neck showing soft-tissue lesion in the right maxillary sinus. The patient is currently under treatment with external beam radiotherapy.

Myeloid sarcoma and extramedullary hematopoiesis expand the spectrum of ERG-positive proliferations: an ancillary tool in the diagnosis

ERG overexpression has been linked to acute myeloid leukemia/myeloid sarcoma (MS). The aim of our study was to identify the frequency of ERG immunohistochemical (IHC) expression in MS (n = 21), blastic plasmacytoid dendritic cell neoplasms (BPDCNs; n = 8), extramedullary hematopoiesis (EMH: n = 9), normal and pathological bone marrow trephine biopsies (BM-TBs, n = 18), and the marrow component of adrenal myelolipomas (n = 15). ERG-positive and ERG-negative immunostains were identified in 68.4% and 31.5% of patients with MS, respectively (2–3+, 20% to >90% of cells), while all BPDCNs were negative. ERG + MS cases were over-represented in those of myeloid differentiation when compared with those of pure monocytic/monoblastic differentiation, which were ERG-negative (P=<0.001). ERG was expressed in immature myeloid cells in 100% of cases of EMH, BM-TBs, and adrenal myelolipomas (n = 42), resulting in a sensitivity of 100% in this setting. Negative ERG immunostaining was also 100% sensitive in discriminating cells of erythroid lineage, mature lymphocytes, and reactive or neoplastic plasma cells. Variable IHC expression occurred in megakaryocytes and neutrophils. In summary, we confirmed a high frequency of ERG expression in MS and identified ubiquitous expression in non-neoplastic immature myeloid lineage cells. We believe that ERG can be of diagnostic utility to identify neoplastic and reactive myeloid infiltrates in peripheral tissues and possibly as an ancillary marker to exclude the diagnosis of BPDCNs when positive. However, ERG must be used in an antibody panel, as expression is not limited to myeloid cells.

Use of Ultrasensitive RNA In Situ Hybridization for Determining Clonality in Cutaneous B-Cell Lymphomas and Lymphoid Hyperplasia Decreases Subsequent Use of Molecular Testing and Is Cost-effective.

Primary cutaneous B-cell lymphomas (PCBCLs) are diagnostically challenging entities due to significant overlap in clinical and morphologic features with reactive lymphoid proliferations. Traditional methods for evaluating clonality such as immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) are limited by low sensitivity, which leads to additional costly and time-consuming molecular clonality assays. More recent technology has introduced ultrasensitive bright-field RNA in situ hybridization (BRISH) to the field, which can detect single molecules of light-chain mRNA. The current study evaluated 274 cases of PCBCL in addition to atypical and reactive lymphoid infiltrates, with CISH or BRISH performed on 180 (65.7%). CISH was performed on 105 (58.3%), and BRISH was performed on 75 (41.7%). Significantly fewer immunoglobulin heavy-chain (IGH) rearrangement studies were performed on cases that were evaluated with BRISH as compared with CISH (P=0.02). Subgroup analysis demonstrated that cases with restriction by BRISH were significantly less likely to have subsequent IGH studies performed (P=0.01). The expected costs of cases using CISH versus BRISH were $1053.89 versus $810.32 to the patient and $245.63 versus $225.23 to the laboratory. The use of ultrasensitive BRISH to evaluate clonality in PCBCL reduced the use of IGH rearrangement studies when compared with CISH. In particular, cases with light-chain restriction by BRISH did not result in confirmatory molecular testing. Despite slightly higher costs to the laboratory to perform BRISH, routine use of this methodology can result in cost savings to both the patient and laboratory by decreasing the use of expensive molecular methods.

Comparison of longitudinal SARS-CoV-2 nasopharyngeal specimens reveals the transcriptomic COVIDome

Introduction/ObjectiveSARS-Cov-2 is well established to introduce a cytokine-like storm among select individuals that results in multisystem failure and death. Comorbidities, age, oxygen status, and real-time appraisal of inflammatory markers in the blood have been used to risk stratify patients, however, these clinical markers do not comprehensively characterize the at-risk population or disease course. To understand the molecular underpinnings of the primary site of SARS-CoV-2 infection, here, we interrogated the transcriptomic profile of the nasopharyngeal tissue among paired SARS-CoV-2 specimens.Methods/Case ReportWe performed ribosomal depletion RNAseq on 24 primary samples, including 16 paired samples from 8 unique patients who converted between SARS-CoV-2 negative and positive status via clinical diagnostic qRT-PCR. Additional targeted qRT-PCR was performed for ACE2 and TMPRSS2 in an extension sample of 54 paired specimens from 27 unique patients who converted in their SARS-CoV-2 status on the basis of the qRT- PCR test. Differential gene expression, differential correlative expression with ACE2, and correlative expression with viral load was used to identify genes, which were integral to SARS-CoV-2 pathogenesis, so termed the COVIDome. Gene ontologies, pathways, and reactive infiltrate was assessed between specimens and compared with measures of clinical outcome using regression with appropriate correction for multiple hypotheses.Results (if a Case Study enter NA)We observed significant enrichment for ontologies of lymphocyte activation, specifically interferon gamma signaling; (P<1E-20) and platelet activation (P<1E-5). Genes specifically enriched across all three modules included: ADAMDEC1, EPSTI1, GRIP2, IRF7, KLHDC7B, OAS3, OASL, PIK3R4, RSAD2, and XAF1. Using CIBERSORT to approximate immune cell populations from bulk RNA, we observed and enrichment for CD4 immune cells, which was associated with viral status (P<0.01) while high-risk gene signatures were associated with measures of clinical outcome (P<0.05).ConclusionWe characterized the pathogenesis of SARS-CoV-2 in longitudinal nasopharyngeal samples of COVID- 19 patients and related these molecular manifestations with measures of clinical outcome. As proof of principal, our findings suggest additional study in a large, longitudinal extension sample is warranted to validate and assess molecular features of clinical outcome associated with SARS-CoV-2 infection.

Rare presentation of primary hepatic marginal zone B-cell lymphoma and membranous glomerulopathy in a 3-year-old boy

Abstract Introduction/Objective Primary hepatic marginal zone B-cell lymphoma (MZL) is a rare entity that has been described with chronic inflammatory disorders such as chronic viral hepatitides B and C and primary biliary cholangitis. We report MZL in a 3-year-old African-American boy that was discovered incidentally at autopsy. Methods/Case Report The patient first came to medical attention at 9-months of age with bilateral periorbital edema that progressed to generalized edema of the[PL1] face, extremities, and abdomen. Laboratory testing showed nephrotic syndrome with massive proteinuria (50-60 g/day). A percutaneous renal biopsy specimen showed membranous glomerulopathy with PLA2R detected by immunofluorescence, and granular IgG deposition along tubular basement membranes. Serum was negative for anti-PLA2R antibodies. The patient suffered recurrent upper respiratory tract infections requiring several intensive care hospitalizations. At 3 years of age, he was transported unresponsive and pulseless to the emergency department where he was pronounced dead. A brother with the infantile nephrotic syndrome had died from sepsis at 2 years of age. Suspicion of abuse led to an autopsy by the medical examiner, who discovered nodular masses in the right and left liver lobes, which histologically showed a serpiginous infiltrate of small B-lymphocytes positive for CD20, CD43 admixed with plasmacytoid cells with kappa light chain restriction. There were no extrahepatic tumors. Transmission electron microscopy of glomeruli showed membranous glomerulopathy. Kidneys showed dense reactive interstitial lymphocytic infiltrate with germinal centers Results (if a Case Study enter NA) NA Conclusion To our knowledge, this is the first reported case of MZL presenting in a pediatric patient with membranous glomerulopathy. Both diagnoses are associated with autoimmune diseases and persistent, chronic inflammation. Recurrent infections in this patient suggest an immunoregulatory disorder, setting the stage for chronic inflammation, as seen in the kidney, with progression to MZL in the liver.

Un pseudolymphome mixte chez une femme sous tamoxifène : un réel défi étiologique

We report a case of cutaneous pseudolymphoma of the nose following herpes in a patient on tamoxifen. A 53-year-old patient, treated for a breast tumor under tamoxifen, had presented a firm nodule in the nose 1 month before consulting. The interrogation revealed a history of nasolabial herpes which had resolved a few days before. Skin biopsy and immunohistochemistry revealed a reactive mixed lymphoid infiltrate. The rest of the patient's biological assessment was negative. The evolution was marked by spontaneous regression of the nodule. The originality of our observation lies in the rarity of the association of a pseudolymphoma with a herpes infection. The majority of pseudolymphomas are idiopathic and their course is generally marked by spontaneous regression of the lesions. The spontaneous regression of the lesion despite the continuation of tamoxifen, in our patient, seems to be an element in favor of the imputability of the herpes virus in the occurrence of the pseudolymphoma. Received: March 8th, 2021 Accepted: July 1st, 2021

26380 A case of cutaneous T-cell pseudolymphoma within a tattoo

A 53-year-old female with a history of systemic lupus erythematosus, hypertension, and diabetes mellitus type 2 presented with a 4-year history of red, pruritic nodules at the site of a tattoo originally placed 25 years prior on the right lower leg. Treatment with intralesional corticosteroids for 8 months led to improvement of the lesion and associated itch; however, the lesion recurred after discontinuation of the therapy. Physical examination revealed two 3-4 cm firm, erythematous to hyperpigmented smooth nodules confined to the red pigmented sites within the tattoo on the right lower anterior extremity. A punch biopsy demonstrated irregular epidermal acanthosis and spongiosis with exocytosis of lymphocytes into the epidermis. A diffuse dermal infiltrate of small lymphocytes with admixed plasma cells, histiocytes, and foamy giant cells was observed involving a fibrotic dermis and extending into the subcutis. A methenamine silver stain and Fite were negative. On immunohistochemical staining, the infiltrate predominantly expressed CD3+ with a few scattered CD20+ B-cells. A diagnosis of cutaneous T-cell pseudolymphoma was made. The patient was subsequently referred to plastic surgery where she underwent a full excision with split-thickness skin graft. We present this case of pseudolymphoma within a tattoo to highlight that tattoo ink is a risk factor for adverse immunological reactions including cutaneous pseudolymphoma. Pseudolymphoma is a rare benign reactive inflammatory infiltrate that often clinically and histologically mimics cutaneous lymphoma. The reaction inflammatory cell infiltrate can be predominantly T-cell or B-cell or mixed. Early recognition and skin biopsy is imperative for proper diagnosis and management.

Lymphoepithelial carcinoma of the larynx: An unusual response to EXTREME regimen therapy. A new option for treatment?

Lymphoepithelial Carcinoma (LEC), an aggressive variant of Squamous Cell Carcinoma (SCC), is an undifferentiated carcinoma with an intermixed reactive lymphoplasmacytic infiltrate. Most cases of LEC occur in the nasopharynx, while it rarely involves other sites. LEC of larynx and hypopharynx is an extremely rare and aggressive neoplasm, characterized by a high propensity to loco-regional dissemination and a poor prognosis; it represents the 0,2% of all tumours of the larynx. Since it is such a rare tumor, the current literature provides only recommendations and there are no treatment guidelines available. A 70-year-old man with laryngeal LEC and both distant and nodal metastases was treated with chemotherapy, following EXTREME regimen therapy. It was classified as a cT3 N3b M1 glottic cancer (Stage IVC, AJCC 8th Ed.), stage IVC. As the response on metastases was unexpectedly encouraging, surgical treatment on T could be performed. Patient underwent to total laryngectomy and bilateral neck dissection. To date, eight months after surgery, the patient is disease free. The unusual clinical course is reported.

Progressive Histiocytosis of Non-Epitheliotropic Dendritic Cells in a Feline

Background: Histiocytic tumors in felines are nodules that commonly develop on limbs and head extremities. They can be divided into many subtypes including cutaneous histiocytoma, histiocytic sarcoma, reactive fibrohistiocytic nodule, Langerhans cell histiocytosis, and progressive feline dendritic cell. Despite the same origin, they have behaviors that differ from each other, thus it is important to confirm diagnosis with histopathological and immunohistochemical tests, because early identification can facilitate prognosis and treatment. In this study, we describe the pathological and immunohistochemical characteristics, enabling differentiation feline neoplasms derived from histiocytes. Case: A 5-year-old, crossbreed, male, feline presented with a nodulation at the base of the left ear. The mass was slow growing, partially alopecic, with no other changes associated with tumor development. The nodule was round and circumscribed, movable, with an elevated surface. He was referred for surgery and an elliptical sample around the tumor was carefully dissected. Routine histopathological evaluation was performed with hematoxylin and eosin (HE), as well as immunohistochemistry. Histopathology showed circumscribed proliferation of histiocytic cells, with abundant and eosinophilic cytoplasm. The proliferative cells were large and rounded, extending from the superficial dermis and basement membrane to the deep dermis. At the extremities, some cells had visible vacuoles. Mitotic activity ranged from 3 to 4 mitoses per field in 40x magnification. Immunohistochemistry showed positive staining for histocompatibility complex MCII and lysozyme antibodies, marking histiocytic cells. Labeling was positive for CD20 in cells of lymphoid lineage B and negative for E-cadherin. Histiocytic cells did not invade the epidermis; hence, proliferation was classified as nonepitheliotropic. These methods contribute to the literature regarding the diagnosis of this rare tumor. Therefore, histological as well as immunohistochemical evaluation are important bfor confirming clinical diagnosis of histiocytic proliferation non-epitheliotropic. Discussion: Progressive histiocytosis of feline dendritic cells, in both epitheliotropic and non-epitheliotropic forms, is considered a clinically progressive and rare disorder. There are reports which include cytological, clinical, histological and immunohistochemical examinations, but the diagnostic characteristics regarding the non-epitheliotropic classification have not yet been properly identified. Nodulations are predominantly observed in head and limb regions, usually non-ulcerated, which can both increase and decrease in size, and are typically painless. The tumor in the present case was restricted to the base of the ear and no evidence of infiltration or metastasis was found. Progressive histiocytosis may spread and reach the lymphatic system through the lymph nodes, subsequently becoming systemic. The non-aggressive behavior observed in this case is possibly related to the non-epitheliotropic pattern. In the present case, MHC II histocompatibility complex markers, a phenotype compatible with dendritic cells, were used. Lysozyme antibodies marked histiocytic cells and the reactive lymphoid infiltrate was composed of CD20-positive B lymphoid lineage cells. Staining for E-cadherin was negative, negative results in labeling experiments is common, it is dependent upon the cellular origin of the leukocytes present in the sample. Staining for these molecules is recommended for differentiating feline progressive histiocytosis from Langerhans cells. Langerhans cells can be characterized by E-cadherin expression in about 10% of cases and marked T lymphocyte and neutrophil expression in the affected tissue. In this case, the histopathological exam along with immunohistochemistry was essential for differentiating them.