H pylori-Negative MALT-Associated Extranodal Marginal Zone Lymphoma: A Comprehensive Case Report and Literature Review.

Extranodal marginal zone B-cell lymphoma (ENMZL) of mucosa-associated lymphoid tissue (MALT), a rare subtype of B-cell lymphoma, is typically associated with Helicobacter pylori (H pylori) infection, especially in gastric cases. However, this article presents 2 unique cases of H pylori-negative colonic ENMZL, challenging the conventional understanding of the disease. The first case involves an 80-year-old male diagnosed with Stage 1E ENMZL in the descending colon, and the second describes a 74-year-old male with sigmoid colon ENMZL. Both cases lacked H pylori infection, adding complexity to their management. Accompanying these case studies is a comprehensive literature review, delving into the epidemiology, pathology, clinical features, diagnosis, and treatment of H pylori-negative ENMZL, with a focus on gastrointestinal involvement. This review highlights the importance of considering H pylori-negative cases in ENMZL diagnosis and management, illustrating the need for further research and individualized treatment approaches in this uncommon lymphoma subtype.

Histological criteria for selecting patients who need clonality test for non-gastric MALT lymphoma diagnosis.

The histological diagnosis of extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is difficult for pathologists. Recently, digital pathology systems have been widely used to provide tools that can objectively measure lesions on slides. In this study, we measured the extent of marginal zone expansion in suspected MALT lymphoma cases and compared the results with those of a molecular clonality test. In total, 115 patients who underwent an IGH gene rearrangement test for suspected MALT lymphoma were included in this study. All cases were histologically classified into three patterns; "small lymphoid aggregates with no germinal center (Pattern 1)," "lymphoid follicles with germinal center (Pattern 2)" and " fused marginal zone or diffuse small lymphocytic proliferation (Pattern 3)." The proportions of monoclonality in Pattern 1, 2, and 3 were 25.0%, 55.0%, and 97.9%, respectively. The ratios of marginal zone thickness to germinal center diameter and entire lymphoid follicle area to germinal center area were measured in Pattern 2 cases using a digital pathology system. Combining the width cutoff of 1.5 and the areal cutoff of 3.5, the sensitivity, specificity, positive predictive value, and negative predictive value for MALT lymphoma were 96.97%, 70.37%, 80.00%, and 95.00%, respectively. In conclusion, through objective measurement of the marginal zone, suspected cases of MALT lymphoma requiring a molecular clonality test can be effectively selected.

[Interpretation of histiocytic/dendritic cell neoplasms and stromal-derived neoplasms of lymphoid tissues in the 5th edition of WHO classification of haematolymphoid tumors].

The 5th edition of the World Health Organization classification of hematolymphoid tumors (WHO Blue Book) is soon to be published. Significant revisions have been made in the chapters on histiocytic/dendritic cell neoplasms and stroma-derived neoplasms of lymphoid tissues, leading to the reclassification and renaming of specific diseases. This article provides a concise interpretation and summary of these updates, highlighting the differences from the fourth edition. Pertinent changes from clinical pathological diagnosis to treatment and prognosis are explored, with an emphasis on recent advancements in molecular genetics. Newly introduced disease classifications are discussed, and the section on follicular dendritic cell sarcoma contributed by the author is detailed to assist readers in quickly understanding and assimilating the new classification standards.

Primary central nervous system marginal zone lymphoma.

Marginal zone lymphoma (MZL) is the most common indolent lymphoma primarily arising in the central nervous system (CNS). To date, 207 cases of primary CNS MZL (PCNSMZL) were published, mostly as single case reports or small case series. It most commonly presents as extra-axial dural-based masses, more frequently in middle-aged women, displaying an insidious onset, with a long history of symptoms preceding the diagnosis. PCNSMZL can be radiographically mistaken for meningioma. PCNSMZL consists of CD20+ , CD3- small B lymphocytes with varying degrees of plasmacytic differentiation and low proliferation index. Trisomy 3, but not MALT1 or IgH translocation, is a common genetic abnormality. Other recurrent genetic abnormalities involve TNFAIP3 and NOTCH2. Ethiopathogenesis was poorly investigated. Due to its rarity, standard of care remains to be defined; it exhibits an excellent prognosis after varied treatments, such as surgery, radiotherapy, chemotherapy or their combinations. Nevertheless, each treatment should be considered after an accurate analysis of overtreatment risk. Short follow-up is a major limitation in reported PCNSMZL cases, which restrains our knowledge on long-term results and iatrogenic sequels. This review was focussed on presentation, differential diagnoses, pathological findings, treatment options and clinical outcomes of PCNSMZL; recommendations for best clinical practice are provided.

Adenotonsillar pathology in mucopolysaccharidoses - lysosomal storage predominates in paracortical CD63+ cells.

Despite the adenoids are regularly removed in patients with mucopolysaccharidoses (MPS), the underlying tissue and cellular pathologies remain understudied. We characterized an (immuno)histopathologic and ultrastructural phenotype dominated by lysosomal storage changes in a specific subset of adenotonsillar paracortical cells in 8 MPS patients (3 MPS I, 3 MPS II, and 2 MPS IIIA). These abnormal cells were effectively detected by an antibody targeting the lysosomal membrane tetraspanin CD63. Important, CD63+ storage vacuoles in these cells lacked the monocytes/macrophages lysosomal marker CD68. Such a distinct patterning of CD63 and CD68 was not present in a patient with infantile neurovisceral variant of acid sphingomyelinase deficiency. The CD63+ storage pathology was absent in two MPS I patients who either received enzyme-replacement therapy or underwent hematopoietic stem cells transplantation prior the adenoidectomy. Our study demonstrates novel features of lysosomal storage patterning and suggests diagnostic utility of CD63 detection in adenotonsillar lymphoid tissue of MPS patients.

Tertiary lymphoid structures, a historical reappraisal.

Tertiary lymphoid structures (TLSs) are accumulations of lymphoid cells within non-lymphoid organs that share the cellular compartments, spatial organization, vasculature, chemokines, and function with secondary lymphoid organs, especially lymph nodes. TLSs are organized into a separate T cell and B cell compartments which contain germinal centers with follicular dendritic cells. In most cases, TLSs contain Peripheral Node addressin (PNAD) expressing high endothelial venules (HEVs). TLSs have been described in various mouse models of inflammation and are associated with a wide range of autoimmune diseases. Other than these, TLSs have been described in chronic allograft rejection and cancer.

Introduction to the Fifth Edition of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues.

The World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues has been the internationally accepted standard for over 20 years. The fifth edition of the WHO Classification (WHO-HEM5) is a multidisciplinary effort by pathologists, clinicians and other specialists that builds upon the revised fourth edition published in 2017. Entities in WHO-HEM5 are organized hierarchically. There are several changes in WHO-HEM5 from the previous edition, including addition of new entities, deletion of some entities and recognition or revision of some subtypes reflecting scientific developments and clinical advances during the past few years. Essential and desirable criteria for each entity are included. Here we introduce WHO-HEM5. Four reviews will follow that emphasize important aspects of the classification.

[WHO classification of tumors of hematopoietic and lymphoid tissues, 2022 (5th edition): lymphoid tumors]. / Klassifikatsiya VOZ opukholei gemopoeticheskoi i limfoidnoi tkanei, 2022 g. (5-e izdanie): opukholi limfoidnoi tkani.

The paper discusses changes in the structure of the classification, criteria for the diagnosis of lymphoid neoplasms in the 5th edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (2022). Changes are presented regarding new nosological units, renaming and abolition of some previously existing ones. The importance of molecular genetic studies in the isolation of many lymphomas and the need to apply these studies in everyday clinical practice are emphasized. Lymphoid precancerous processes and lymphoid proliferations introduced into the Classification for the first time are considered.

Cellular Immune Responses in Lymphoid Tissues of Broiler Chickens Experimentally Infected with Necrotic Enteritis-Producing Clostridium perfringens Strains.

Host cellular responses against Clostridium perfringens (CP), the causative agent of necrotic enteritis (NE) in chickens, are poorly understood. In the present study, we first tested the NE-producing ability of seven netB+ CP strains (CP5, CP18, CP26, CP64, CP67, CP68, and NCNE-1), using an experimental infection model of broiler chickens. Evaluation of intestinal gross lesions showed that all the strains, except CP5, were able to produce NE, while CP26 and CP64 strains produced relatively more severe lesions when compared with other groups. Next, cellular responses in the cecal tonsil (CT), bursa of Fabricius, and spleen were evaluated in chickens infected with strains representing variation in the level of virulence, namely, avirulent CP5, virulent CP18, and a relatively more virulent CP26 strain. Immunophenotyping analysis showed that CT or splenic macrophage frequencies were significantly higher in CP18- and CP26-infected chickens compared with uninfected controls, while the frequencies of γδ T-cells and B-cells in the CT of CP26-infected chickens were significantly higher than those in the uninfected, CP5- or CP18-infected groups. The T-cell analysis showed that chickens infected with CP18 and CP26 had a significantly higher number of splenic CD4+ and CD8+ T-cells expressing CD44 and CD28 activation molecules, while CP26-infected chickens also had significantly increased CT frequency of these activated CD4+ and CD8+ T-cells when compared with uninfected or CP5-infected groups. Collectively, our findings suggested that cellular responses, including activation of T-cells, are selectively induced against virulent CP strains and that the NE-producing characteristics of this pathogen may influence the outcome of immunity to NE.

Respuestas inmunes celulares en tejidos linfoides de pollos de engorde infectados experimentalmente con cepas de Clostridium perfringens productoras de enteritis necrótica. Las respuestas celulares del huésped contra Clostridium perfringens (CP), el agente causante de la enteritis necrótica (NE) en pollos, son poco conocidas. En el presente estudio, primero se analizó la capacidad de producción de enteritis necrótica de siete cepas de C. perfringens netB+ (CP5, CP18, CP26, CP64, CP67, CP68 y NCNE-1), utilizando un modelo de infección experimental de pollos de engorde. La evaluación de las lesiones macroscópicas intestinales mostró que todas las cepas, excepto CP5, podían producir enteritis necrótica, mientras que las cepas CP26 y CP64 produjeron lesiones relativamente más severas en comparación con los otros grupos. Posteriormente, se evaluaron las respuestas celulares en las tonsilas cecales (CT), la bolsa de Fabricio y en el bazo de pollos infectados con cepas que representan variaciones en el nivel de virulencia, por ejemplo las cepas CP5 avirulenta, CP18 virulenta y la cepa CP26 relativamente más virulenta. El análisis de inmunofenotipado mostró que las frecuencias de los macrófagos esplénicos o de las tonsilas cecales fueron significativamente más altas en los pollos infectados con las cepas CP18 y CP26 en comparación con los controles no infectados, mientras que las frecuencias de células T γd y células B en tonsilas cecales de los pollos infectados con la cepa CP26 fueron significativamente más altas que las de los pollos de los grupos no infectados, o infectados con las cepas CP5 o CP18. El análisis de células T mostró que los pollos infectados con las cepas CP18 y CP26 tenían un número significativamente mayor de células esplénicas T CD4+ y CD8+ que expresaban moléculas de activación CD44 y CD28, mientras que los pollos infectados con la cepa CP26 también tenían una frecuencia significativamente mayor en las tonsilas cecales de estas células T CD4+ y CD8+ activadas en comparación con grupos no infectados o infectados con la cepa CP5. En conjunto, estos hallazgos sugirieron que las respuestas celulares, incluida la activación de las células T, se inducen selectivamente contra las cepas virulentas de C. perfringens y que las características productoras de enteritis necrótica de este patógeno pueden influir en el resultado de la inmunidad contra la enteritis necrótica.

Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach: A clinicopathologic analysis.

OBJECTIVES: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is historically associated with Helicobacter pylori (HP) infections in more than 80% of patients. However, the incidence of HP-negative MALT lymphoma has been increasing. The clinicopathologic features have not been well studied, and optimal management strategies remain unclear. METHODS: The pathology database was searched for primary gastric MALT lymphomas diagnosed from 2000 to 2017. The clinical data and the slides were reviewed. The cases were divided for analysis into those with a background of chronic gastritis with HP, chronic gastritis without HP, and without either a background of chronic gastritis or HP. RESULTS: Of 70 gastric MALT lymphoma cases identified, 26 (37% of total) had chronic gastritis and were positive for HP histologically (n = 23) or were HP positive by additional laboratory testing (n = 3). The remaining 44 (63% of total) cases were HP negative by histology. Within the HP-negative cases, 5 (11% of HP-negative cases) showed histologic gastritis while 39 (89% of HP-negative cases) did not have sufficient evidence of gastritis through review of slides (n = 18) or based on available pathology reports (n = 21). The HP-negative cases without gastritis had higher propensities to show a mass lesion on endoscopy compared with HP-positive cases (37.5% vs 11.1%, P = .02) at the initial diagnosis. The immunophenotype and rate of positive B-cell gene rearrangement were not significantly different between the 2 groups. While all HP-positive patients received antibiotics for HP eradication, treatment in the HP-negative group varied among antibiotics, radiation, rituximab, or chemotherapy. Among HP-negative patients with available follow-up, 13 (39%) showed disease recurrence, similar to the recurrence rate in HP-positive patients; however, no individual from either group has died of the disease thus far. CONCLUSIONS: The incidence of HP-negative MALT lymphoma is increasing, and in our practice, it is currently more common than HP-associated MALT lymphomas. The pathophysiology of HP-negative MALT lymphoma without chronic gastritis remains unclear. Follow-up data in our study suggest that the prognosis of these cases is excellent despite varied management modalities.

Radiological and pathological analysis of the galaxy sign in patients with pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma.

BACKGROUND: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma sometimes presents as large pulmonary nodules composed of small nodular opacities (galaxy sign) on computed tomography (CT). The aim of this study was to assess the presence, usefulness, and pathological characteristics of the galaxy sign on CT of pulmonary MALT lymphoma. METHODS: From January 2011 to December 2021, chest CTs of 43 patients with pulmonary MALT lymphoma were reviewed by two radiologists for the galaxy sign and various other findings. Interreader agreement to characterize the galaxy sign and factors associated in making a correct first impression on CT prior to pathological diagnosis were assessed. Resected specimens were reviewed by two pathologists, and the proportion of peripheral lymphoma infiltrates was compared between lesions with and without the galaxy sign. RESULTS: Of 43 patients, 22 patients (44.2%) showed the galaxy sign (κ = 0.768, p < 0.0001). The galaxy sign (p = 0.010) was associated with making a correct first impression on CT prior to pathological diagnosis. On pathological examination, lesions showing the galaxy sign on CT demonstrated a significantly higher proportion of peripheral lymphoma infiltrates (p = 0.001). CONCLUSION: The galaxy sign can be seen on CT of pulmonary MALT lymphoma with a higher proportion of peripheral lymphoma infiltrates and may be useful in making a correct diagnosis of pulmonary MALT lymphoma.

Adenoid hypertrophy in children: a narrative review of pathogenesis and clinical relevance.

Adenoids (nasopharyngeal tonsils), being part of Waldeyer's ring, are masses of lymphoid tissues located at the junction of the roof and the posterior wall of the nasopharynx. Adenoids play an important role in the development of the immune system and serve as a defence against infections, being the first organs that come into contact with respiratory and digestive antigens. The causes of adenoid hypertrophy are not fully known. They are most likely associated with aberrant immune reactions, infections, environmental exposures and hormonal or genetic factors. The aim of this review is to summarise the current knowledge of adenoid hypertrophy in children and associated diseases. Adenoid hypertrophy has many clinical manifestations that are frequent in the paediatric population and is accompanied by various comorbidities.

Risk factors analysis and establishment of predictive nomogram of extranodal B-cell lymphoma of mucosal-associated lymphoid tissue.

PURPOSE: The role of radiation therapy in mucosa-associated lymphoid tissue (MALT) lymphoma is poorly defined. The objective of this study was to explore the factors associated with the performance of radiotherapy and to assess its prognostic impact in patients with MALT lymphoma. PATIENTS AND METHODS: Patients with MALT lymphoma diagnosed between 1992 and 2017 were identified in the US Surveillance, Epidemiology, and End Results database (SEER). Factors associated with the delivery of radiotherapy were assessed by chi-square test. Overall survival (OS) and lymphoma-specific survival (LSS) were compared between patients with and without radiotherapy, using Cox proportional hazard regression models, in patients with early stage as well as those with advanced stage. RESULTS: Of the 10,344 patients identified with a diagnosis of MALT lymphoma, 33.6% had received radiotherapy; this rate was 38.9% for stage I/II patients and 12.0% for stage III/IV patients, respectively. Older patients and those who already received primary surgery or chemotherapy had a significantly lower rate of receiving radiotherapy, regardless of lymphoma stage. After univariate and multivariate analysis, radiotherapy was associated with improved OS and LSS in patients with stage I/II (HR=0.71 [0.65-0.78]) and (HR=0.66 [0.59-0.74]), respectively, but not in patients with stage III/IV (HR=1.01 [0.80-1.26]) and (HR=0.93 [0.67-1.29]). The nomogram built from the significant prognostic factors associated with overall survival of stage I/II patients had a good concordance (C-index=0.749±0.002). CONCLUSION: This cohort study shows that radiotherapy is significantly associated with a better prognosis in patients with early but not advanced MALT lymphoma. Prospective studies are needed to confirm the prognostic impact of radiotherapy in patients with MALT lymphoma.

Gut-associated Lymphoid Tissue/Dome-Type Carcinoma of the Colon: A Rare Case Report With Review of the Literature.

Gut-associated lymphoid tissue (GALT) carcinoma, also termed dome-type carcinoma, is an infrequent distinctive subtype of colorectal adenocarcinoma and only 18 cases have been reported in the English medical literature. These tumors have unique clinicopathological features and are considered to have a low malignant potential with favorable prognosis. Herein, we described a case of a 49-year-old male with intermittent hematochezia for 2 years. Colonoscopy revealed a sessile broad-based polyp of approximately 20 mm × 17 mm in the sigmoid colon 260 mm away from the anus, with a slightly hyperemic surface. Histologically, this lesion showed typical GALT carcinoma. The patient was followed up for one and a half year and he did not experience any discomfort, such as abdominal pain or hematochezia, and no tumor recurrence occurred. Moreover, we reviewed the literature, summarized the clinicopathological features of GALT carcinoma, and highlighted its pathological differential diagnosis to further explore this infrequent type of colorectal adenocarcinoma.

Immunohistochemical analysis of arachidonate 5-lipoxygenase expression in B-cell lymphomas: Implication for B cell differentiation and its analogy with lymphomagenesis.

Arachidonate 5-lipoxygenase (ALOX5) is a cardinal enzyme in the synthesis of leukotrienes, which are powerful immune-regulating lipid mediators. We previously reported that ALOX5 is preferentially expressed in B lymphocytes in the mantle zone of human lymphoid tissue. In the context of physiological relevance, the loss of the Alox5 gene in mice significantly impairs the development of follicular B helper T cells and antibody production. However, ALOX5 expression in B-cell lymphomas has not been investigated in detail. In this study, we examined ALOX5 expression in representative B-cell lymphomas and non-neoplastic lymphoid tissues by immunohistochemistry with a commercially available anti-ALOX5 antibody that can be used on formalin-fixed paraffin-embedded specimens. Interestingly, 22/22 cases of mantle cell lymphoma, 7/7 cases of chronic lymphocytic leukemia/small cell lymphoma, and 20/20 cases of follicular lymphoma expressed ALOX5. A small proportion of extranodal marginal zone lymphoma/mucosa-associated lymphoid tissue lymphoma or nodal marginal zone lymphoma cases were positive for ALOX5 (2/13 or 1/3, respectively). In contrast, no cases with diffuse large B-cell lymphoma, regardless of germinal center B cell (GCB) or non-GCB type, expressed ALOX5 (0/25 cases). These findings suggest that ALOX5 may be a novel marker for identifying the cell of origin of B-cell lymphoma. Further investigation is required to clarify the biological significance of ALOX5 expression in lymphoma cells.