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Background: Pseudolymphoma of the liver (reactive lymphoid hyperplasia) (RLH) is a rare condition. It is usually asymptomatic and detected incidentally on radiological imaging. Imaging features are similar to hepatic adenoma, hepatocellular carcinoma, cholangiocarcinoma, and malignant lymphoma and are not specific for pseudolymphoma of the liver. Percutaneous core biopsy is insufficient to distinguish pseudolymphoma of the liver from low-grade malignant lymphoma and extranodal marginal lymphomas. Case Descriptions: In this article, we present a case of hepatic RLH of a patient who was presented with a skin rash on the leg and was detected incidentally on radiological imaging. Conclusion: Preoperative definitive diagnosis of hepatic RLH using various imaging methods, including MRI with hepatocellular agents, is highly difficult.

Objectives In this retrospective study, we report a series of benign lymph nodes showing small populations of normal B-cell precursors characterized by flow cytometry and immunohistochemistry. Methods Ten cases identified during clinical flow cytometry practice were retrospectively reanalyzed with particular attention to hematogone categorization and enumeration. Immunohistochemical staining was performed on five excisional lymph node biopsy specimens to characterize the morphologic correlate. Results Populations of hematogones ranging from 0.13% to 1.86% (median, 0.51%) of all viable leukocytes were demonstrated in 10 benign lymph node samples from eight different patients ranging in age from 17 to 45 years (median, 37.5). These hematogones showed a characteristic immunophenotype (CD19+/CD10+) and maturational pattern by flow cytometry, with progression from stage 1 (median, 0.03%) to stage 2 (median, 0.19%) to stage 3 (median, 0.26%) seen in all cases. Immunohistochemical staining on five excisional biopsy specimens demonstrated a distinct perisinusoidal distribution of CD10+/CD20+ cells with a subset of TdT+ cells, providing a morphologic correlate. Conclusions To our knowledge, this is the first study to characterize distinct hematogone populations within benign lymph nodes by both flow cytometry and immunohistochemistry. Recognizing these normal B-cell precursor populations is important to avoid their miscategorization as a CD10+ B-cell neoplasm.

We present the first and rare case report of syndromic multiple odontogenic keratocysts (OKCs) associated with extensive lymphoid proliferation. A 22-year-old male patient presented with radiolucent lesions in bilateral mandible and maxilla. Histopathology of the lesions showed features of multiple odontogenic keratocysts with reactive lymphoid proliferation. Additionally, presence of calcification of falx cerebri, palmar plantar pits and cervical scoliosis in the patient favored the diagnosis of nevoid basal cell carcinoma syndrome or Gorlin Goltz syndrome. Follow up after 2 years did not show any recurrence. Knowledge of this finding is important so that such entities are not confused with associated lymphoid neoplasms. Presence of lymphoid aggregates may be attributed to associated infection or remnants of cystic lining or breakdown products triggering cell mediated immunity leading to lymphoid hyperplasia.

Epstein-Barr virus (EBV) has been associated with a plethora of neurological manifestations including polyneuropathy and polyradiculopathy. A 27-year-old man with a recent upper respiratory system infection presented with difficulty in walking. His neurological examination revealed reduced muscle strength in both proximal and distal lower limb muscles without sensory and autonomic signs. Needle electromyography showed abnormal spontaneous activity and reduced recruitment of motor units in muscles innervated by multiple lumbo-sacral roots. Cerebrospinal examination showed increased protein levels with normal cell counts. While spinal MRI was normal, whole-body CT and PET examination showed disseminated lymph node enlargement. Anti-EBV viral capsid antigen and anti-nuclear antigen IgG but not IgM was positive, whereas EBV PCR was negative in blood. Analysis of inguinal lymph node biopsy showed reactive lymphoid hyperplasia and EBV DNA. Leucine-rich glioma-inactivated protein 1 (LGI1) antibody was found in serum but not in CSF. All clinical, imaging, and electrophysiological findings improved following steroid and intravenous immunoglobulin treatment. These findings suggested the acute involvement of lumbo-sacral spinal roots and/or motor neurons. Purely motor polyradiculopathy has been reported in both EBV-positive and LGI1 antibody-positive patients, and EBV infection is known to precede different autoimmune manifestations. Whether EBV infection may trigger LGI1 autoimmunity and cause involvement of spinal motor roots and/or motor neurons needs to be further studied.

Las hiperplasias cutaneas linfoides, antiguamente llamadas seudolinfomas cutaneos, son proliferaciones benignas de linfocitos, que simulan linfomas tanto clinica como histologicamente y de acuerdo a su componente celular mas predominante pueden ser clasificados como de celulas B o T. La de celulas B se considera una entidad clinicopatologica especifica, mientras que las de celulas T son un grupo heterogeneo de enfermedades, mas que una enfermedad en si. Dado que no son tan frecuentes no se tienen datos precisos de su epidemiologia. Se presenta caso clinico de paciente de sexo femenino de 45 anos con un nodulo eritematoso y violaceo en la region frontal de mas de un ano de evolucion con reporte histopatologico confirmado por estudios de inmunohistoquimica de hiperplasia cutanea linfoide de celulas B. Rev.cienc.biomed.2011; 2(1): 98-105 PALABRAS CLAVES Seudolinfoma cutaneo. Hiperplasia linfoide. Linfomas. Infiltrados cutaneos. SUMMARY The cutaneous pseudolymphoma and cutaneous lymphoids hyperplasias are benign proliferations of lymphocytes that simulate lymphomas clinically and histologically, wich according to its most prominent cellular component may be of B or T cells. The B-cell pseudolymphoma is considered a distinct clincopathologic entity, while the T is a heretogeneous group of diseases rather than a disease itself. Given its low frequency, there is a lack of accurate data about its epidemiology. This review presents a case of a female patient of 45 years old with an erythematous violaceous nodule in frontal region of more than 1 year of evolution with histopathologic report of B cell pseudolymphoma confirmed by inmunohistochemical studies. Rev.cienc.biomed. 2011; 2(1): 98-105 KEYWORDS Cutaneous pseudolymphoma. Lymphoid hyperplasia. Lymphomas. Cutaneous infiltrates.

Chronic follicular cholecystitis (CFC) is a rare pathology characterized by prominent lymphoid follicles in the lamina propria distributed throughout the gallbladder wall. It has also been mentioned in the literature as lymphoid hyperplasia and pseudolymphoma. CFC represents less than 2% of cholecystectomies. Its etiopathology is mostly unknown. Most reports are based on histopathological findings, with little or no imaging analysis. We describe a case involving a 66-year-old man radiologically diagnosed as xanthogranulomatous cholecystitis (XGC) versus malignancy, revealing CFC with surrounding inflammatory changes in the cholecystectomy specimen.

The luminal gastrointestinal tract can be a site of robust immune response in which reactive lymphoproliferative processes can sometimes be difficult to distinguish from lymphoma. In this article, we review gastrointestinal tract normal resident inflammatory cells and common nonneoplastic lymphoproliferative responses with emphasis on their differential and links to lymphoma. Topics that are covered include lymphocytic esophagitis, gastric chronic inflammation, mucosa-associated lymphoid tissue, and ulceration, small intestinal lymphoid hyperplasia, celiac disease, microscopic colitis, inflammatory bowel disease, primary immunodeficiency, graft-versus-host disease, and anti-programmed cell death protein-1 effect. We additionally present the less common differential of histiocytic processes within the gastrointestinal tract. The aim of this paper is to serve as a reference for practicing pathologists facing lymphoid, lymphoplasmacytic, or histiocytic processes in the luminal gastrointestinal tract. We hope to help the practicing pathologist distinguish benign from malignant entities and identify features requiring further workup.

Micronodular thymic carcinoma with lymphoid hyperplasia (MNTCLH) is a rare form of thymic carcinoma. We present the experience of RYTHMIC, the French national network devoted to the treatment of thymic epithelial tumors through multidisciplinary tumor boards with a review of all tumors by pathologists for classification and staging. Six cases of MNTCLH were diagnosed during a review of 1007 thymic epithelial tumors. Histologically, epithelial cells with atypia and mitoses formed micronodules that were surrounded by an abundant lymphoid background with follicles. There was neither obvious fibro-inflammatory stroma nor necrosis. Spindle cells areas were common. Initial diagnosis was micronodular thymoma in two cases, cellular atypia being overlooked, eclipsed by the micronodular pattern. Immunohistochemistry with a panel of five antibodies showed that cytokeratins (AE1-AE3) and p63-positive epithelial cells also expressed CD5 and that there was no TdT-positive cells within the tumors. CD20 highlighted the lymphoid hyperplasia. Additionally epithelial cells also expressed CD117 and diffusely Glut 1. Twenty-seven micronodular thymomas with lymphoid stroma diagnosed during the same period did not show the CD5 and CD117 positivities seen in MNTCLH and contained TdT-positive lymphocytes. Three of the 6 patients with MNTCLH had adjuvant radiotherapy. Three patients with follow-up information were alive without recurrence at 38, 51, and 95 months. Our study shows that immunohistochemistry, such as that used in the RYTHMIC network with a small panel of antibodies, may easily help to confirm the correct diagnosis of MNTCLH, a rare and low-aggressive form of thymic carcinoma, and avoid the misdiagnosis of micronodular thymoma.

The aim of this study was to reproduce severe pneumonic lesions, similar to those during naturally-occurring porcine respiratory disease complex, in pigs dually inoculated with porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae at 6 weeks of age, followed by inoculation with porcine circovirus type 2 at two weeks after. Time and sequence of infection with three pathogens mirror Asian field conditions. Microscopically, interstitial pneumonia and peribronchiolar lymphoid hyperplasia are considered the most characteristic lung lesions in infected pigs. The results of the present study demonstrate that inoculation of pigs with these three pathogens can lead to severe interstitial pneumonia with peribronchial or peribronchiolar lymphoid hyperplasia and fibrosis.

Introduction: Palatine tonsils are paired masses of lymphoid tissue, which act as an immunologicbarrier against the entry of pathogenic agents into the respiratory and digestive tracts. Tonsillitis is acommon disease, especially among children. Chronic tonsillitis is a disease with repeated attacks ofacute tonsillitis or a sub-clinic form of a resistant or poorly treated infection. Aim: To determine theclinicopathological findings in various lesions of tonsillectomy in the palatine tonsil. Materials andmethods: This is a retrospective study where 105 (Unilateral-20, Bilateral) cases ofhistopathologically identified tonsillectomy specimens as well as 4 tonsillar biopsies were included.The available data for all the patients as regards age, sex, and clinical symptoms were collected.Sections were taken from tonsillectomy specimens from representative areas while tonsillar biopsieswere processed completely. Routine hematoxylin and eosin staining was done along with this specialstain- PAS (periodic acid- Schiff) for actinomycosis and ZN stain for AFB. Results: Amongst thecases, 78 cases showed chronic tonsillitis. 11 cases were chronic tonsillitis with actinomycosis, acutechronic tonsillitis in 07 cases, granulomatous tonsillitis in 03 cases, acute ulcerative tonsillitis withmicroabscesses in 01 case, and reactive lymphoid hyperplasia in 02 cases. Three malignancies wereobserved – Two cases of squamous cell carcinoma and one case of undifferentiatedcarcinoma/lymphoma. Conclusion: Chronic tonsillitis is a common problem facing in all age groups,Histopathology plays a significant role in diagnosing both benign and malignant lesions of the tonsil.

BACKGROUND Reactive lymphoid hyperplasia (RLH) of the liver is a rare liver lesion. It is considered difficult to differentiate radiologically from hepatocellular carcinoma, metastatic liver tumor and other pathologies. CASE SUMMARY A 54-year-old woman presented to our hospital with RLH of the liver. The patient had a diagnosis of metastatic carcinoma of the liver from an unknown origin and subsequently underwent partial hepatectomy. However, histopathological analysis revealed RLH. The lesion showed perinodular enhancement in the arterial phase on contrast-enhanced computed tomography and magnetic resonance imaging. On diffusion-weighted imaging (DWI), we encountered linear hyperintensity along the portal tract consecutive to the liver lesion, which is a new characteristic radiologic finding. This finding corresponded to the lymphoid cell infiltration of the portal tract. Furthermore, there was strongly restricted diffusion on the apparent diffusion coefficient map. We used these characteristic radiologic findings to diagnose the lesion as a lymphoproliferative disease. CONCLUSION The linear hyperintensity consecutive to the liver lesion on DWI provided additional valuable diagnostic information.

Summary The gastrointestinal tract (GI) is the primary site of lymphoproliferative lesions, spanning from reactive lymphoid hyperplasia to overt lymphoma. The diagnosis of these diseases is challenging and an integrated approach based on clinical, morphological, immunohistochemical and molecular data is needed. To reach to confident conclusions, a stepwise approach is highly recommended. Histological evaluation should first assess the benign versus neoplastic nature of a given lymphoid infiltrate. Morphological and phenotypic analyses should then be applied to get to a definite diagnosis. This review addresses the key histological features and diagnostic workup of the most common GI non-Hodgkin lymphomas (NHLs). Differential diagnoses and possible pitfalls are discussed by considering distinct groups of lesions (i.e. small to medium B-cell NHLs; medium to large B-cell NHLs; T-cell NHLs; and mimickers of Hodgkin lymphoma). The key clinical and epidemiological features of each entity are also described.

One of the most misdiagnosed appendicular pathologies is lymphoid hyperplasia (LH) that can be managed con-servatively when identified early and is self-limiting. The aim of this retrospective study was to compare acute appendicitis (AA) with LH in terms of hematological parameters to determine whether there is a hematological predictor to distinguish the two diseases.Complete blood cell counts of patients with AA were compared with those having LH.One-hundred-ninety-five patients (118 male/77 female) underwent appendectomy. Histopathological examination re-vealed acute AA in 161 patients (82.6%), and negative appendectomy (NA) in 19 patients (9.7%). Of the NA specimens, 16 were LH (8.2%). Thirteen patients (6.7%) had AA with simultaneous LH. White blood cell count (p=0.030, neutrophil (p=0.009), neutrophil per-centage (p=0.009), and neutrophil/lymphocyte ratio (p=0.007) were significantly higher in AA whereas lymphocyte count (p=0.027), lymphocyte percentage (p=0.006) were significantly higher in LH. Multi logistic regression analysis revealed white blood cell count as the only independent predictor in distinguishing AA from LH with a 69.1% sensitivity, 80.0% specificity, 77.5% positive predictive value, and 72.1% negative predictive value. The cut-off value for white blood cell count was 11.3 Ku/L, and every one unit (1000/mm3) increase in white blood cell count raises the risk of AA by 1.24 times, while values below this value will increase the likelihood of LH.The most predictive complete blood count parameter in distinguishing LH from AA appears to be as white blood cell count.

Florid lymphoid hyperplasias of the lower female genital tract, also known as pseudolymphoma or lymphoma-like lesions, are benign lesions displaying histologic features which mimic aggressive B-cell lymphomas. Initially described by Young and colleagues in 1985, fewer than 100 cases have been published, making this lesion rather uncommon and subject to misdiagnoses. However, given that this entity has now been included in the World Health Organization's most recent classification, greater clarity would be beneficial for pathologists and physicians. Thus, our report aims to review these entities and provide all available data. We reviewed the available literature according to PRISMA guidelines. We found that lymphoma-like lesions, regardless of their localization, display numerous superficial lymphoid B cells admixed with a polymorphic small lymphocytic and plasmocytic background and, sometimes, superficial ulceration. Large lymphoid cells show prominent nucleoli and mitotic figures. Immunohistochemistry can usually exclude large cell lymphomas, such as high-grade follicular lymphoma and Burkitt lymphoma, when a starry sky pattern is found, as well as Hodgkin Lymphoma; however, the exclusion of diffuse large B-cell lymphoma or marginal zone lymphoma is more difficult. Explorations seeking infectious agents may show Epstein-Barr virus or, rarely, Borrelia burgdorferi involvement. Molecular study occasionally finds a monoclonal B-cell population, but without the subsequent follow-up which would otherwise be worrisome. Despite its somewhat aggressive histologic features, the benignity of this entity must be highlighted to avoid misdiagnosis and complications due to overtreating.

Ectopic thymic carcinomas are rarely diagnosed in the thyroid gland, let alone in extrathyroid tissues. In the currently available literature, only five cases of extrathyroidal malignancies with thymic differentiation have been reported as arising in the major salivary glands. A 69-year-old female presented with a slow-growing palpable mass in the left parotid gland. Fine needle aspiration biopsy suggested metastatic cancer, whereas core needle biopsy revealed high-grade squamous cell carcinoma. The patient underwent left radical parotidectomy with selective ipsilateral lymph node dissection and subsequent radiation therapy. The surgical specimen was taken for histopathological examination. Microscopically, the tumor resembled thymic carcinoma. It was composed of large nests of squamoid cells with smooth contours, focally with a syncytial growth pattern, and accompanied by abundant lymphocytes with reactive lymphoid follicles. This appearance resembled a micronodular thymic carcinoma with lymphoid hyperplasia. Moreover, the tumor displayed expression of squamous markers (p40 and p63) and markers of thymic carcinoma (CD5 and CD117). Therefore, the final diagnosis of intrasalivary thymic carcinoma was rendered. The molecular analysis including next-generation sequencing demonstrated no variants of the strong, potential, or unknown clinical significance. The patient remains disease-free at 1-year follow-up. In the current case, we comprehensively present a clinical, microscopic, molecular, and radiological picture of CD5-positive squamous cell carcinoma of the parotid. We postulate that similar cases should be designated as intrasalivary thymic carcinoma analogically to similar thyroid tumors. Our case and the limited literature data indicate they should be distinguished from conventional squamous cell carcinoma of major salivary glands due to their rather favorable prognosis.

Post-transplant lymphoproliferative disorder (PTLD) and other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are iatrogenic lymphoproliferative disorders (LPD) that develop in association with immunosuppressive treatment in the setting of organ transplantation and autoimmune disease, respectively. Each has a spectrum of pathologies ranging from lymphoid hyperplasia to lymphoma. To clarify the characteristics of the diffuse large B-cell lymphoma (DLBCL) subtype in a cohort of 25 patients with PTLD or OIIA-LPD from our institute, we selected 13 with a histological subtype of DLBCL, including 2 cases of PTLD and 11 of OIIA-LPD. The median patient age at diagnosis was 70 years, with a female predominance. Both PTLD cases developed after kidney transplant. Of the patients with OIIA-LPD, 10 had rheumatoid arthritis, 1 had mixed connective tissue disease, and 8 were treated using methotrexate. Both of the PTLD patients and 6 of the OIIA-LPD patients had extranodal manifestations. All patients except for one were classified as having the non-germinal center B-cell (non-GCB) subtype according to the Hans algorithm. Tissue samples from 8 patients were positive for CD30 and 8 were positive for Epstein-Barr virus (EBV)-encoded small RNA. Seven patients had MYC-positive tissue samples, but none had MYC translocation. Our study suggests that extranodal manifestations and the non-GCB subtype are common, that EBV is associated with the DLBCL subtype of PTLD and OIIA-LPD, and that anti-CD30 therapy is applicable. In addition, our patients with the DLBCL subtype of PTLD and OIIA-LPD exhibited MYC overexpression without MYC translocation, suggesting an alternative mechanism of MYC upregulation.

AimsAngioimmunoblastic T cell lymphoma (AITL) is often misdiagnosed in cytology. Hence, the present study was conducted to identify the distinctive cytomorphological features of AITL in lymph node fine-needle aspirates (LN-FNA).MethodsThis was a 4-year retrospective case–control study. Cases included LN-FNAs from patients with histopathologically confirmed AITL. The controls included LN-FNAs from patients with histopathologically confirmed reactive lymphoid hyperplasia (RLH; n=25). Eleven cytomorphological features were assessed in all the aspirates; the strength of association was determined by OR, Cramer’s V and multiple correspondence analysis (MCA).ResultsOf a total of 22 cases of AITL reported on histopathology, 19 adequate aspirates from 14 patients (63.6%) were available for review. On univariate analysis, 5 of 11 cytomorphological variables were found to be significant for AITL; however, on MCA, 3 of these parameters, viz absence of tingible body macrophages (OR=0.014; V=0.74), presence of atypical lymphoid cells (OR=10.8; V=0.41) and singly scattered epithelioid cells (OR=19.3; V=0.31), were found to be the strongest predictors of AITL.ConclusionsThe absence of tingible body macrophages, presence of atypical lymphoid cells and singly scattered epithelioid cells in polymorphic LN-FNAs are significant cytomorphological predictors of AITL in comparison with RLH. Knowledge of these diagnostic predictors, supplemented by clinicoradiological correlation and appropriate ancillary studies, can help diagnose AITL on aspiration cytology.

Introduction: Nasal extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTCL) is a high-grade Epstein-Barr virus (EBV)-associated malignancy with poor outcomes. There are few biomarkers for the accurate diagnosis and prognostic prediction of the disease. The aim of this study was to investigate the clinicopathological significance of prohibitin (PHB) expression in nasal ENKTCL. Methods: The expression level of PHB was detected via immunohistochemical staining in 49 nasal ENKTCL tissues and age- and sex-matched controls of 30 nasal mucosa-reactive lymphoid hyperplasia (NRLH) tissues. The correlations between the PHB expression and clinicopathological features of patients with nasal ENKTCL were evaluated. Results: The results indicated a significantly decreased expression of PHB in nasal ENKTCL tissues compared with in NRLH tissues. Low-level PHB expression was significantly associated with younger age and fever (p = 0.008 and 0.018, respectively). The Kaplan-Meier analysis showed that the cytoplasm expression level of PHB in nasal ENKTCL was inversely related to overall survival (p = 0.046). Conclusions: PHB may be a potential diagnostic marker and prognostic predictor of nasal ENKTCL.

Background Micronodular thymic tumors with lymphoid stroma include micronodular thymoma with lymphoid stroma (MNT) and micronodular thymic carcinoma with lymphoid hyperplasia (MNC), whose micromorphological features are lymphoid stromal hyperplasia and nodular arrangement of tumor epithelial cells. This type of tumor is rare; therefore, the corresponding clinical guidelines, histopathological diagnostic criteria, prognostic factors, and therapeutic regimens have not been established. Case summary This study covers a novel presentation of MNC in a patient and summarizes the clinicopathological characteristics of this type of tumor by using pooled-analysis methods. Morphologically, this tumor type is a series of benign to malignant pedigrees. We establish the following criteria for the classification of micronodular thymic tumors with lymphoid stroma: (1) Tumor cells with moderate-to-severe dysplasia; (2) Tumor cell mitotic figures > 2/10 high-power fields; (3) Appearance of neoplastic necrosis; (4) No terminal deoxynucleotidyl transferase-positive immature T lymphocytes within the tumor; (5) Tumor cells with a Ki-67 index ≥ 10%; and (6) Tumor cells express CD5. Cases that fall into the borders of two categories in terms of morphology are attributed to atypical MNT. It is proposed that the diagnosis of MNT should be established on the diagnostic criteria mentioned above. Conclusion Our diagnostic algorithm can effectively distinguish malignant tumors from benign tumors and provides a potent basis for predicting a prognosis, which offers a practical reference for oncologists and pathologists.

Combination therapy with ipilimumab and nivolumab is an adjuvant treatment approach for metastatic melanoma that boasts increased 3-year survival when compared with a single immunotherapy agent. Combination therapy, however, is associated with increased toxicities, especially cutaneous side-effects. Here we present a patient with metastatic melanoma and a sudden eruption of painful nodules on the face and arms 10 days after the administration of the fourth dose of combination ipilimumab/nivolumab. Biopsies demonstrated lymphoid hyperplasia, not clinically or pathologically consistent with an infectious, malignant or autoimmune etiology; a diagnosis of pseudolymphoma secondary to ipilimumab/nivolumab was made. After a steroid taper, the lesions resolved, and the patient was restarted on nivolumab monotherapy 2 weeks later without recurrence of symptoms or disease.

PurposeLymphoid hyperplasia can be an important mimicker of acute appendicitis by creating a non-compressible appendix more than 6 mm in diameter. The aim of this study was to evaluate methods of distinguishing lymphoid hyperplasia and appendicitis on the basis of sonography, lamina propria thickness, and Alvarado scoring.MethodsThis retrospective study included 259 patients (142 appendicitis, 117 lymphoid hyperplasia). The US (ultrasound) reports of the patients were reviewed and the maximum diameter of the appendix, the presence or absence of increased echogenicity of the surrounding pericaecal fat, local fluid collection, the presence of reactive lymph nodes in the periappendiceal area, and mural hyperemia within the appendix were recorded.ResultsThe use of additional sonographic criteria, lamina propria thickness (≤1 mm is indicative for appendicitis), or Alvarado scoring (>6 mm is indicative for appendicitis) provided a true-positive diagnosis for acute appendicitis.ConclusionThe presence of local fluid collection in the periappendiceal area and a lamina propria thickness ≤ 1 mm are the most successful parameters for distinguishing appendicitis from lymphoid hyperplasia.

Castleman’s disease (CD) or angiofollicular lymph node hyperplasia includes a heterogeneous mix of reactive lymphoproliferative processes with well-defined histological features. However, they differ in their localization patterns, clinical expression and etiopathogenesis. There are 4 types, one of them is the multicentric CD that is not associated with any viruses and has recently been called idiopathic MCD (iMCD). iMCD is a lymphoproliferative disorder with specific histopathological characteristics, more than one region of affected lymph nodes and absence of infection associated to human herpesvirus 8 and human immunodeficiency virus (HIV). iMCD covers multiple differential diagnoses and might simulate autoimmune diseases such as systemic lupus erythematosus. The aim of this article is to report the case of a patient with Castleman’s disease and lupus-like presentation. We present the case of a 38-year-old man without morbid history, who presented lumbago, fever, diaphoresis and asthenia with two months of evolution, associated to bilateral cervical adenopathies. General examinations result negative, antinuclear antibodies at a dilution of 1/640 were positive, and extractable nuclear antigens were positive suggesting moderate Systemic Lupus Erythematosus (SLE) plus secondary Sjögren’s. Methylprednisolone and Hydroxycloroquine boli were thus initiated. The patient evolved with anasarca, severe anemia, acidosis, polyserositis and multiple mediastinal adenopathies. Immunoglobulin and cyclophosphamide were thus initiated. He later presented fever, thrombocytopenia and nephrotic syndrome. Biopsy of cervical lymph node reported lymphadenitis with polyclonal plasmacytosis and concentric lymphoid hyperplasia, in agreement with iMCD. Treatment with Rituximab was initiated, which led to the favorable evolution of the patient. iMCD is a systemic inflammatory disease, its presentation corresponds to a constitutional syndrome resulting in a wide differential diagnosis. Every time suspicious adenopathies appear, they must be biopsied since this might lead to a definitive diagnosis.

Hepatic pseudolymphoma is a very rare benign reactive lymphoid hyperplasia associated with autoimmunity and chronic inflammatory liver diseases such as primary biliary cirrhosis and may mimic hepatocellular carcinoma. This diagnosis should be suspected in female with a suspicious single tumor. Close monitoring is needed in view of its premalignant nature.

Introduction: The lymph node biopsy plays an important role in establishing the cause of lymphadenopathy. The distribution of lymphomas is varied in different geographic regions. The 2016 revision World Health Organization classification of lymphoid neoplasms is used to classify lymphomas. Aims: To study retrospectively the spectrum of histopathological diagnosis in lymph nodes at our institution, diagnostic utility of immunohistochemical markers in the subtyping of both nodal and extranodal lymphomas and to correlate the histopathology and immunohistochemistry. Materials and Methods: We retrospectively reviewed lymph nodes between 2012 and 2017, analysed the distribution of cases and classified lymphoma according to the revised 2016 World Health Organization classification of lymphoid neoplasms and compared with other studies. Results: The distribution of various cases from 235 lymph nodes were as follows: 27% of granulomatous lymphadenitis, 25% of reactive lymphoid hyperplasia, 24% of metastatic deposit, 17% of lymphoma, and 7% of miscellaneous category that included progressive transformation of germinal centres, Kimuras disease, extramedullary hematopoiesis, kikuchi lymphadenitis, neuroendocrine tumor, schwannoma. B-cell lymphomas outnumbered T- cell lymphomas. The statistical parameters were compared between histopathology and immunohistochemistry. Sensitivity, specificity, diagnostic accuracy, positive predictive value and negative predictive value were calculated. Conclusions: Lymph node biopsy helps in establishing the cause of lymph node enlargement. The distribution of lymphomas in India is varied when compared to the rest of the world. Immunohistochemistry plays an important role in subtyping lymphomas. Keywords: Lymphoma, WHO classification, Immunohistochemistry, Lymph node.

Objectives: Histopathological examination of lymph node is one of the gold standard test for the diagnosis of neoplastic and non-neoplastic lesions, as lymphadenopathy is a common presentation of large variety of disorders including benign and malignant. This study aims at identifying various histopathological lesions of lymph node, their patterns and frequency of occurrence. Materials and Methods: This retrospective study includes 70 histopathologically diagnosed cases of lymph node biopsies received by the department of pathology, Dr. B.R. Ambedkar Medical College, Bengaluru from Jan 2017 to Aug 2018. Lymph nodes sent along with known primary malignant resection specimens were excluded from the study. Results: Out of 70 cases, non-neoplastic lesions were more common comprising of 57 cases (81.5%) and neoplastic lesions were 13 cases (18.5%).Non-neoplastic lesions included tuberculous lymphadenitis 27cases (38.5%), non-specific reactive hyperplasia 25 cases (35.7%), specific reactive lymphadenitis 3 cases (4.2%) and other granulomatous lesions 2 cases(2.8%). Neoplastic lesions included metastasis 7 cases (10%), Hodgkin’s lymphoma 5 cases (7.1%) and non-Hodgkin’s lymphoma 1 case (1.4%). Conclusion: Non-neoplastic diseases were more common than neoplastic diseases. Among non-neoplastic, tuberculous lymphadenitis was the most common lesion and among neoplastic lesions, metastasis was more common. Keywords: Tuberculous lymphadenitis, Metastasis, Reactive lymphoid hyperplasia, Hodgkin lymphoma, Lymphadenopathy.

Introduction: Pathomorphological changes in the lungs, stomach, and small intestines of wild boars infected with Metastrongylus spp., Ascarops strongylina, and Macracanthorhynchus hirudinaceus were investigated. Material and Methods: Dissection of 11 wild boars was performed, and parasitised organs were histologically investigated by common techniques. Results: Macroscopic lesions in the lungs infected with Metastrongyus spp. were seen within the apical parts of the large lobes, irregular in form, pale greyish in colour, and compact in consistency. The main pathohistological findings were: the presence of parasite forms, and lymphocytes and neutrophils in the lumen of bronchi and bronchioles, desquamation of the bronchial and bronchiolar epithelium, emphysema, thickening of alveolar septa, hyperaemia, alveolitis, infiltration of the interstitial tissue with giant cell, monocytes and eosinophils, and peribronchial and disseminated lymphoid hyperplasia. The principal observations accompanying infection with A. strongylina were inflammation and focal mucosal damage in the stomach, the latter clearly demarcated from the surrounding tissues. Severe injuries in the place of attachment of M. hirudinaceus to the wall of the small intestine were seen. Intestinal villi, underlying mucosa, and submucosa were destroyed, and an intense inflammatory reaction was present. Conclusion: The histopathological lesions showed wide diversity, varying from mild to severe; but none of them were lethal.

We present a case whereby standard immunohistochemistry and flow cytometry studies for a conjunctival biopsy were unable to reliably differentiate between the two distinct pathological processes of benign reactive lymphoid hyperplasia from conjunctival lymphoma. A tissue diagnosis was only able to be conclusively attained after the application of immunoglobulin heavy chain rearrangement studies to the specimen. This is unusual and to our knowledge has not been previously expressed in the literature. Hence, the use of these further molecular studies may have great potential clinical implications in helping resolve such diagnostic dilemmas.

Magnetic resonance imaging shows an en plaque mass lesion with homogenous enhancement (A). Hematoxylin and eosin (HE) staining shows dura matter with multiple lymphoid follicular structures; large interfollicular areas are also seen. Germinal center with polymorphic lymphoid blast cells as well as a sharply demarcated mantle zone with small lymphocytic cells could be clearly distinguished (B). Reactive activated B cells (centroblasts), centocytes and tingible body macrophages are seen in the germinal center, HE staining (C). Germinal center revealed predominance of the B-cells, CD20-Staining (D). CD3-staining shows multiple T lymphocytes in the mantle zone (E). Bcl-2 positive B cells are seen exclusively in the mantle zone of the follicle. Scale bar 100 µm (F).

Introduction Primary cutaneous marginal zone B-cell lymphoma (MZL) follows an indolent clinical course. Histopathologically, there is a polymorphous infiltrate that includes small lymphocyte-like and centrocyte-like B cells and plasma cells usually with a substantial T-cell fraction. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, in which the signature cells have a follicular T-helper (TFH) phenotype and are admixed with numerous B cells. Thus, both present histologies of combined B-cell and T-cell infiltrates and represent differential diagnoses. The presence of TFH in MZL has yet to be elucidated. Methods Forty-one biopsies from 40 cases of MZL and 7 cases of lymphoid hyperplasia cutis (LCH) were stained with antibodies to follicular T-helper cells, including Bcl-6, PD-1, ICOS, and CD10, as part of their diagnostic workup, were reviewed, and the stained slides were evaluated semiquantitively. Five reactive lymph nodes were also evaluated as controls. Results All cases of MZL and LCH contained TFH, albeit usually in low proportions. There were repeated differences in levels of expression between TFH markers, with PD1 and Bcl-6 being the most prevalent. The pattern of involvement in MZL and LCH closely mirrored that observed in the reactive lymph nodes. Conclusion MZL includes TFH cells, similar to reactive lymph nodes, and a complexity of cell types. This provides evidence of an organoid immune response challenging its simple categorization as a malignancy.

Purpose The lacrimal caruncle is composed of numerous structures including different glands as well as hair follicles. Accordingly, the spectrum of benign and malignant lesions is broad, and the clinical diagnosis is often challenging. Here we systematically analyzed excised caruncular tumors over the past 22 years with special emphasis on the clinico-pathological correlation to provide a guidance for clinicians. Methods Retrospective evaluation with clinico-pathologic correlation of surgically removed caruncular tumors between 1998 and 2020 at a tertiary referral center. Results Eighty-two caruncular tumors were identified in the respective period. The patients were between 11 and 85 years of age (mean, 46.8 years; median, 49 years). Nevi (n = 35), cystic lesions (n = 14), oncocytoma (n = 9), papilloma (n = 8), sebaceous gland hyperplasia (n = 8), and reactive lymphoid hyperplasia (n = 4) were observed most frequently. Besides, we are the first reporting herniated orbital fat accompanied by a pyogenic granuloma. 2.4% (n = 2) were malignant tumors (sebaceous gland carcinoma, conjunctival intraepithelial neoplasia with pyogenic granuloma). Conclusion Caruncular tumors show a broad spectrum of mostly benign tumors. They can occur in patients of any age. However, 8/9 oncocytomas and both malignant lesions were detected in patients older than 60 years. Although the clinical diagnosis was confirmed in only 68.3% by the histopathological analysis, the two malignant lesions were identified as such already clinically. Caruncular lesions with a history of growth or other signs of malignancy should be excised followed by detailed histopathological examination to allow a final diagnosis and exclude rare malignant tumors with lethal potential.

Background In Fine-needle aspiration cytology (FNAC) of lymph nodes, tissue fragments derived from follicular structures may be observed in specimens. We defined such tissue fragments as follicular tissue fragments (FTF), and investigated differences in cytological findings for FTFs of each histological type. Method A total of 41 cases with FNAC of lymph nodes were examined. In these cases, the histopathological diagnoses were reactive lymphoid hyperplasia (RLH) (n = 17), follicular lymphoma (FL) (n = 13), diffuse large B-cell lymphoma (DLBCL) (n = 18), and Burkitt lymphoma (n = 1). Specimens were analyzed for the presence of FTFs, and for tingible-body macrophages (TBMs) and monomorphism of lymphocytes in FTFs. FTFs with a maximum diameter of >500 μm were defined as large-FTFs. Results FTFs were identified in RLH (14/17, 82.4%), FL (13/13, 100%), and DLBCL (3/18, 16.7%). In the RLH subtypes, FTFs were present only in follicular hyperplasia (FH) (14/15, 93.3%) and not in paracortical hyperplasia (0/2). The number of cases with large FTFs among those with FTFs were as follows: RLH (10/14, 71.4%), FL (11/13, 84.6%), and DLBCL (0/3). Similarly, those with TBMs in FTFs were as follows: RLH (13/14, 92.9%), FL (0/13) and DLBCL (2/3, 66.7%). Monomorphism was observed in RLH (1/14, 7.1%) and FL (11/13, 84.6%), but not in DLBCL (0/3). Conclusions Distinction between FL and FH is possible by identifying large-FTFs. In FL, TBMs are absent in FTFs and lymphocytes often show monomorphism. Therefore, recognizing FTFs and observing details inside the FTFs are useful for identification and differential diagnosis of FL and FH in FNAC of lymph nodes.

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by gain-of-function (GOF) mutations in PIK3CD or PIK3R1 genes. The phenotypes of APDS are highly variable, ranging from asymptomatic adults to profound immunodeficiency causing early death in childhood. Herein, we reported two pediatric patients with APDS presented with recurrent lung infections, sinusitis, hematuria, and positive anti-neutrophil cytoplasmic antibody (ANCA), previously diagnosed as granulomatosis with polyangiitis (GPA). Bronchoscopy showed mucosal nodule lymphoid hyperplasia in the entire airway. Many inflammatory cells infiltrated around the airway and in the lung parenchyma, and numbers of CD3+ T cells and CD20+ B cells were significantly increased, especially CD3+ T cells. Whole exome sequencing showed that they had the E1021K (c.3061 G >A) mutation in the PIK3CD gene. These are the first reported cases of APDS presenting as childhood-onset GPA. Pediatricians should suspect of APDS in the differential diagnosis of children who present with GPA-like symptoms. Additionally, timely and repeated bronchoscopies could contribute to providing an important diagnostic clue for APDS.

Background First described in 1955 Primary mediastinal seminomas are rare. Only 1–4% of mediastinal tumours are germ cell tumors; majority of which are teratomas. They typically present in men aged between 20 and 40 years. Very few cases are reported in the literature. Florid follicular lymphoid hyperplasia can obscure the malignant cells and is a rarer finding still. We present a rare case of a 48 year old man with a primary mediastinal seminoma with florid follicular lymphoid hyperplasia; found following excision of a clinically presumed thymoma. Case presentation A 48 year old man was referred for excision of a thymic mass. The presumed diagnosis was a thymoma; following preoperative investigations. The mass was incidentally found on a radiological imaging. However, the patient did report mid-sternal discomfort on lying flat and breathlessness. The patient underwent a thymectomy via a partial median sternotomy with good recovery. Histological assessment was that the mass was in fact a primary mediastinal seminoma with florid follicular lymphoid hyperplasia. A primary testicular malignancy was excluded and the patient required no further oncological treatment. Conclusions Only 11 cases have previously been reported of primary mediastinal seminoma with florid follicular lymphoid hyperplasia. Although rare, a primary mediastinal seminoma should be considered as a differential diagnosis for presentations with a thymic mass. Tumour markers can be helpful, however are only positive in third of cases. Ultrasound imaging of the gonads is essential to exclude a primary gonadal lesion. Pure seminomas are radiotherapy and chemotherapy sensitive however the mainstay treatment of primary mediastinal seminomas remains surgical excision. Radiotherapy is reserved postoperatively for incomplete surgical margins.

Lymphoproliferative lesions that have morphology between benign and malignant are difficult to diagnoseeven with immunohistochemical and clonality testing. The correct diagnosis is necessary for the prompttreatment. These lesions can also serve as instructive models of lymphomagenesis. FOXP1 plays an importantrole in B-cell development, has a potential oncogene in B-cell Non-Hodgkin lymphoma, and p53 proteinhas a crucial role in the regulation of cell cycle, DNA repair, apoptosis, and senescence tumor suppressionactivity. In this study, we analyze the role of FOXP1 and p53 expression in reactive lymphoid hyperplasiaand B-cell Non-Hodgkin lymphoma, large cell type. 68 paraffin blocks samples from patients diagnosedas reactive lymphoid hyperplasia and B-cell Non-Hodgkin lymphoma, large cell type was sectioned andstained with immunohistochemistry for FOXP1 and p53, and the percentage of nuclear cells showingpositive staining were evaluated. Expression of FOXP1 and p53 in B-cell Non-Hodgkin lymphoma, largecell type is higher than in reactive lymphoid hyperplasia with p=0.001 and cutoff point 45%(CI=95%) forFOXP1 and p=0.001 and cutoff point 7.5%(CI=95%) for p53. There is a significant correlation between theexpression of FOXP1 and p53 in reactive lymphoid hyperplasia and B-cell Non-Hodgkin lymphoma, largecell type (p=0.001). Our findings suggest that high expression of FOXP1 and p53 in B-cell Non-Hodgkinlymphoma may demonstrate the role of FOXP1 and p53 in lymphomagenesis and these markers may helpto distinguish benign and malignant lymphoproliferative lesions.

Background Subcutaneous vaccination or desensitization may induce persistent nodules at the injection sites. Without the knowledge of prior injection, histological work-up may be challenging. Objective Aim of this study was to contribute to the histological work-up of unclear subcutaneous nodules, especially their differentiation from cutaneous lymphoma. Methods We retrospectively reviewed clinical data and histological slides of four patients with subcutaneous nodules, which were suspected to suffer from cutaneous T- or B-cell lymphoma. Sections of these cases and 12 negative controls were stained with hematoxylin and eosin and a standardized immunohistochemical panel of B- and T-cell markers including EBER in situ-hybridization as well as electron microscopy. Results In all cases, large histiocytes with granular cytoplasm being compatible with intracellular aluminum hydroxide were present. EBER in situ-hybridization revealed positive staining of these granular histiocytes while staining was absent in negative controls. Limitations Post hoc completion of medical history revealed that vaccination or specific immunotherapy had been applied before at the biopsy site in only three out of four patients; one patient was lost to follow-up. Conclusion EBER in situ-hybridization is an adjunctive tool to differentiate aluminum-induced granuloma/lymphoid hyperplasia from other forms of pseudolymphoma and cutaneous B- or T-cell lymphomas. This article is protected by copyright. All rights reserved.

Background Pulmonary hamartomas are the most common benign tumors of the lungs and can occur anywhere in the lungs, normal hyperplasia, congenital malformation, inflammatory changes, and tumorigenesis are hypothesized to underlie the pathogeny, but the definite etiology remains to be elucidated. Primary pulmonary lymphoma (PPL) refers to clonal lymphoid hyperplasia of one or both lungs in patients who have no detectable extrapulmonary lymphoma or bone marrow involvement at the time of diagnosis and during the subsequent 3 months. It is rare for both diseases to occur in the lungs of the same patient. Methods Appropriate laboratory tests, Chest CT scan, bronchoscopy and CT-guided percutaneous lung biopsy. Results Laboratory tests showed (1-3)-β-D-glucan was 226.3 pg/mL and sputum culture of Aspergillus niger. Chest Computer Tomography (CT) scan showed multiple flaky high-density shadows in both lungs, proven to be right hamartoma with left lung pulmonary primary lymphoma by bronchoscopy biopsy and CT guided percutaneous needle lung biopsy. Conclusions When there are high density shadows or nodules in different parts of one patient's lung, these lesions may not be the same disease. Therefore, it is necessary to conduct biopsies of the lesions in different parts of the lung.

HIV-related lymphoid hyperplasia has been exceptionally described outside lymph nodes. To our knowledge, 3 cases of nasopharyngeal localisation have been described in the literature. We report here an intracranial localisation with an important ophthalmological clinical impact. Our observation allows us to approach the differential diagnoses of intracranial lesions in the HIV-positive patient, to analyse the differential diagnoses of benign lymphoid hyperplasia and to discuss the therapeutic options.

A 34-year-old woman presented with abdominal pain for 2 months. Abdominal CT revealed a large bezoar in the distal ileum with surrounding thickened ileal wall and enlarged mesentery lymph nodes. On FDG PET/CT, the thickened ileal wall and enlarged mesentery lymph nodes showed increased FDG uptake. Ileal malignancy with mesentery lymph node metastasis was suspected. The distal ileum and enlarged mesentery lymph nodes were removed. Benign ileal ulcer and mesentery reactive lymphoid hyperplasia were confirmed by histopathology.

High-throughput RNA sequencing (RNA-seq) uses massive parallel sequencing technology, allowing the unbiased analysis of genome-wide transcription levels and tumor mutation status. Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) is a fibroinflammatory disease characterized by the enlargement of the ocular adnexal tissues. We analyzed RNA expression levels via RNA-seq in the biopsy specimens of three patients diagnosed with IgG4-ROD. Mucosa-associated lymphoid tissue (MALT) lymphoma, reactive lymphoid hyperplasia (RLH), normal lacrimal gland tissue, and adjacent adipose tissue were used as the controls (n = 3 each). RNA-seq was performed using the NextSeq 500 system, and genes with |fold change| &ge, 2 and p &lt, 0.05 relative to the controls were defined as differentially expressed genes (DEGs) in IgG4-ROD. To validate the results of RNA-seq, real-time polymerase chain reaction (PCR) was performed in 30 IgG4-ROD and 30 orbital MALT lymphoma tissue samples. RNA-seq identified 35 up-regulated genes, including matrix metallopeptidase 12 (MMP12) and secreted phosphoprotein 1 (SPP1), in IgG4-ROD tissues when compared to all the controls. Many pathways related to the immune system were included when compared to all the controls. Expressions of MMP12 and SPP1 in IgG4-ROD tissues were confirmed by real-time PCR and immunohistochemistry. In conclusion, we identified novel DEGs, including those associated with extracellular matrix degradation, fibrosis, and inflammation, in IgG4-ROD biopsy specimens. These data provide new insights into molecular pathogenetic mechanisms and may contribute to the development of new biomarkers for diagnosis and molecular targeted drugs.

Indolent T-lymphoblastic proliferation (iT-LBP) is the extrathymic proliferation of nonclonal TdT + T cells and is typically associated with lymphoid disorders. Although one study revealed that iT-LBP occurred in angioimmunoblastic T-cell lymphoma, no other lymphoma-related cases have been reported. Here, we report three cases of concurrent iT-LBP and benign or malignant lymphoid disorders. The first patient had bilateral cervical lymph node enlargement, and the resected lymph node showed polyclonal precursor T-cells distributed between benign hyperplastic lymphoid follicles. In the second case, iT-LBP occurred in peripheral T-cell lymphoma with a follicular growth pattern, showing that precursor T-cells were distributed between neoplastic follicles composed of CD4 + and CXCL13 + T-cells. In the third case, polyclonal precursor T-cells were distributed between the neoplastic follicles of follicular lymphoma. In summary, our results indicate an association between iT-LBP and reactive lymphoid hyperplasia (case 1) and lymphoma (cases 2 and 3).

Interstitial lung disease (ILD) is an important non-infectious complication in several primary immune deficiencies. In common variable immune deficiency (CVID) it is associated with complex clinical phenotypes and adverse outcomes. The histology of ILD in CVID is heterogeneous and mixed patterns are frequently observed within a single biopsy, including non-necrotising granulomatous inflammation, lymphoid interstitial pneumonitis, lymphoid hyperplasia, follicular bronchiolitis, organizing pneumonia, and interstitial fibrosis; ILD has to be differentiated from lymphoma. The term granulomatous-lymphocytic interstitial lung disease (GLILD), coined to describe the histopathological findings within the lungs of patients with CVID with or without multisystem granulomata, is somewhat controversial as pulmonary granulomata are not always present on histology and the nature of infiltrating lymphocytes is variable. In this mini review we summarize the literature on the histology of CVID-related ILD and discuss some of the factors that may contribute to the inter- and intra- patient variability in the histological patterns reported. Finally, we highlight areas for future development. In particular, there is a need for standardization of histological assessments and reporting, together with a better understanding of the immunopathogenesis of CVID-related ILD to resolve the apparent heterogeneity of ILD in this setting and guide the selection of rational targeted therapies in different patients.