Extranodal Marginal Zone Lymphoma Research Articles

The fifth edition of the WHO-Classification - what is new for cutaneous lymphomas?

The recently published 5th edition of the "World Health Organization classification of hematolymphoid tumors: lymphoid neoplasms" provides a hierarchical reorganization. In general, new (definitive) entities as well as tumor-like lesions were included. Primary cutaneous B-cell lymphomas (CBCL) received a thorough review. A new class/family of cutaneous follicle center lymphomas was defined. Primary cutaneous marginal zone lymphoma is now presented as a separate entity independent from extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. In primary cutaneous T-cell lymphoma, former provisional entities were upgraded to definite entities. Sézary Syndrome was sorted into the class/family of mature T-cell and NK-cell leukemias. Additionally, a newly formed entity of primary cutaneous peripheral T-cell lymphoma, NOS was created for CTCL entities that do not fit into the already described CTCL entities. The increasing importance of genomic and molecular data has already been recognized in classifying leukemias and systemic lymphomas. However, in PCL the genomic landscape has not yet been fully described and validated. Therefore, future research is necessary to describe the genomic and molecular mechanisms underlying the disease entities more clearly. This would both meet a diagnostic need and valuably contribute to future classification schemes.

The Use of Ibrutinib in Extranodal Marginal Zone Lymphoma of the Ocular Adnexa with Multifocal Disease that is Refractory to Rituximab

Tumors of the ocular adnexa been well documented. The most common ocular adnexal lymphoma is extranodalmarginal zone B-cell lymphoma (EMZL), with about a quarter of those occurring in the conjunctiva. We present acase with a patient suspected ocular EMZL, confirmed with biopsy. Positron emission tomography (PET) scan wasperformed to evaluate for distal lesions and the patient was found to have multiple hypermetabolic lesionsthroughout the body. Treatment with rituximab was initiated, and after four weekly treatments, subsequent PETscan showed that the original hypermetabolic lesions remained and new lesions appeared. Rituximab was stoppedand ibrutinib started. After eight months of ibrutinib treatment, PET scan showed that the original hypermetaboliclesions had disappeared. 19 months from initiation of treatment, a new hilar lesion was found. This progressedinto bilateral hilar and mediastinal lymphadenopathy, which was seen on PET scan performed 29 months intotreatment. These findings remained stable 35 months post-initiation of treatment. The use of ibrutinib in thispatient that initially presented with a lesion in the conjunctiva resulted in an initial resolution of the originalsystemic hypermetabolic regions on PET scan. While more studies are needed on ibrutinib in the treatment ofocular EMZL, physicians should be aware of the presentation of this disease and the range of treatment modalities.

Long-term survival outcomes of 'watch and wait' in patients with bronchus-associated lymphoid tissue lymphoma: a multicenter real-world data analysis in Korea.

Bronchus-associated lymphoid tissue (BALT) is a rare cause of extranodal marginal zone lymphoma (MZL). Although most patients with BALT lymphoma (BALToma) show an indolent clinical course and are monitored without treatment, there are limited real-world data on the long-term outcome of "watch-and-wait' strategy in comparison with other treatments.The survival outcomes of patients newly diagnosed with BALToma at three tertiary hospitals in Korea undergoing two treatment strategies were analyzed: group A, patients who were monitored without any treatment or received only radiotherapy after diagnosis; and group B, patients receiving any kind of systemic chemotherapy after diagnosis, regardless of their history of any local treatment such as surgery or radiotherapy.Of the 67 patients included in our analysis, the 10-year progression-free survival (PFS) and 10-year overall survival (OS) rates were 65.3% and 83.2%, respectively. The 10-year PFS rates for observation or localized treatment and systemic chemotherapy were 78.7% and 56.9%, respectively (p = 0.044). Ten-year OS rates for observation or localized treatment and systemic chemotherapy were 100% and 71.7%, respectively (p = 0.016). Multivariate analysis showed that bilateral lung (HR 2.462, p = 0.047) and extrapulmonary organ (HR 4.485, p = 0.004) involvement were the only significant factors associated with poor PFS. Prognostic factor analysis for OS did not yield significant results.Patients with BALToma show a favorable prognosis, suggesting that observation or localized therapy alone may be effective for patient management. However, patients with bilateral lung or extrapulmonary involvement may require careful monitoring for disease progression and more aggressive treatment approaches.

Revealing the clinical impact of MTOR and ARID2 gene mutations on MALT lymphoma of the alimentary canal using targeted sequencing

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are a group of diseases with marked heterogeneity, including clinical, immunohistochemical, and molecular heterogeneity. The disease remains unspecified in the genetic landscape with only a few sequencing studies to date; however, systematic studies of alimentary canal MALT lymphoma have not been reported. To better understand the genetics of this tumor, targeted sequencing in a group of 31 cases (including 2 esophageal, 2 colonic, 4 small intestinal, and 23 gastric cases) and two cases of lymph node hyperplasiawere performed. We found epigenetic regulation (DNMT3A, KMT2D, KMT2A, EP300, TET2, etc.), signaling pathways (APC, CHD8, TNFAIP3, TNFRSF14, ZAP70, NF1,), and tumor suppressor genes (TP53, BCORL1, FOXO1, ATM, etc.) involved. Moreover, we found MTOR gene mutations in 16% of the cases that made these patients more prone to recurrence and metastasis than those with MTOR wild type genes. More interestingly, ARID2 mutations were detected in 32% of all the cases, and the mutation rate was higher and statistically significant in Helicobacter pylori (Hp)-negative patients in the gastric group. Therefore, this study found that MTOR and ARID2 gene mutations have pathogenic and prognostic implications.

Extranodal marginal zone lymphoma of the larynx: A case report and scoping review.

This scoping review aims to review cases of extranodal marginal zone lymphoma (MZL) of the larynx to establish best management practices for this rare clinical entity. In this paper, we report a case of laryngeal MZL, in accordance with CARE guidelines. We then performed a scoping review according to PRISMA-ScR criteria of published cases of MZL involving the larynx. The following data were collected for each case: age, sex, size, location(s) involved, stage, treatment, follow-up, and recurrence duration. Sixty-six patients with laryngeal MZL, first reported in 1990, were identified. Characterized by its low-grade histological appearance and indolent course, laryngeal MZL is generally confined to the larynx and has an excellent prognosis with radiation used as first-line therapy. It is imperative for clinicians to consider lymphoma in the differential diagnosis of a laryngeal tumor from any subsite, as certain pathologies may carry high risks of metastasis.

Salivary gland amyloidosis: Proteomic identification and clinicopathologic characterization of 57 cases

Salivary gland amyloidosis is an uncommon diagnosis. Most studies have focused on minor salivary gland biopsies as a surrogate site for diagnosing systemic amyloidosis, while only few studies have investigated major salivary gland amyloidosis. We retrospectively identified 57 major and minor salivary gland amyloidosis cases typed using a proteomics-based method between 2010 and 2022. Frequency of amyloid types, clinicopathologic features, and distribution patterns of amyloid deposits were assessed. The indication for salivary gland biopsy/resection (known in 34 cases) included suspected amyloidosis (N = 14; 41.2%), lesion/mass (N = 12; 35.3%), swelling/enlargement (N = 5; 14.7%), and rule out Sjogren syndrome (N = 3; 8.8%). Concurrent pathology was reported in 16 cases, and included chronic sialadenitis (N = 11), extranodal marginal zone lymphoma (N = 3), plasma cell neoplasm (N = 1), and pleomorphic adenoma (N = 1). We identified 3 types of amyloidosis: immunoglobulin light chain/AL (N = 47; 82.5%); immunoglobulin heavy chain/AH (N = 1; 1.8%), and transthyretin/ATTR (N = 9; 15.8%). The patterns of amyloid deposits (assessed in 35 cases) included: 1) Perivascular and/or periductal distribution (N = 18; 51.4%); 2) Mass formation (N = 9; 25.7%); 3) Stromal micronodule formation (N = 7; 20.0%); and 4) Diffuse interstitial involvement (N = 1; 2.9%). We also identified one case of AL amyloidosis localized to the major salivary gland, where only 6 other cases with adequate staging workup to exclude systemic amyloidosis were previously reported. In conclusion, salivary gland amyloidosis is an uncommon diagnosis but may be underrecognized due to low index of suspicion. Most cases of salivary gland amyloidosis are AL type, but a minority are ATTR. Therefore, proteomics-based typing remains essential for treatment and prognosis.

Concurrent primary extranodal marginal zone lymphoma and malakoplakia in the vagina: pearls and pitfalls

Primary lymphomas of the female genital tract are rare, representing approximately 1% of extranodal lymphomas. The most common histological subtype is diffuse large B-cell lymphoma, followed by follicular lymphoma. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the female genital tract is rare and usually discovered incidentally. While MALT lymphoma is often linked to infections or autoimmune diseases, its cause in the female genital tract is generally unknown. On the other hand, malakoplakia is a chronic inflammatory condition resulting from an impaired histiocytic response to common bacterial infections. In this report, we present an extremely rare case of concurrent primary MALT lymphoma and malakoplakia in the vagina of a 79-year-old woman who exhibited postmenopausal bleeding and a soft tissue mass. Tissue examination revealed malignant lymphoid cells obscured by abundant inflammatory cells interspersed with numerous blood vessels, mimicking granulation tissue. A significant diagnostic challenge lies initially in missing the concurrent presence of malignant lymphoma and malakoplakia. Therefore, we emphasize the importance of clinicopathological correlation to accurately diagnose these rare conditions.

Indolent B-cell non-Hodgkin lymphomas in children: high association with inborn errors of immunity

Indolent lymphomas are rare in children and mostly consist of pediatric type follicular (PTFL) and pediatric marginal zone lymphomas (PMZL) and extranodal marginal zone lymphoma (ENMZL). Twenty children with indolent lymphoma (10 PTFL, 6 PMZL, 3 ENMZL, 1 mixed type) among 307 Non-Hodgkin Lymphoma (NHL) were retrospectively evaluated. The mean age of the entire group was 10.4 ± 4.4 and was significantly lower in PTFL than in PMZL. Seven patients (35%) had an associated inborn error of immunity (IEI) which was higher than that seen in aggressive lymphomas (5.9%) (p < 0.0001). Seventeen patients (85%) had stage I/II disease. Two patients received no treatment after surgery. Eleven patients were treated only with 3-6 courses of rituximab. Four patients received 3-6 courses of R-CHOP protocol. The prognosis was excellent Five years overall and event-free survivals were 100% and 85%, respectively.

Risk of transformation by frontline management in follicular and marginal zone lymphomas: a US population–based analysis

AbstractFollicular lymphoma (FL) and marginal zone lymphoma (MZL) often have long overall survival (OS), however, high-grade transformation (HGT) to diffuse large B-cell lymphoma markedly reduces survival. The roles of upfront treatment vs observation on the incidence and outcome of HGT remain unclear. Thus, we analyzed a Surveillance, Epidemiology, and End Results database to address this question. Patients diagnosed with FL grades 1 to 2 or MZL between 2000 and 2020 were included. Fine-Gray models estimated the impact of covariates on HGT cumulative incidence and lymphoma-specific survival (LSS) and Cox regression on OS. HGT occurred in 4.2% of 23 384 patients with FL and 2.5% of 20 530 patients with MZL. The 5- and 10-year HGT cumulative incidence rates were 2.80% and 4.87% for FL, and 1.74% and 2.95% for MZL, respectively, which are notably lower than in earlier studies. The annual HGT incidence rate peaked in the first 2 years, then steadily declined over 2 decades for FL and all MZL subtypes. In FL, upfront observation vs treatment increases HGT risk (sub-distribution hazard ratio [SHR], 1.23; 95% confidence interval [CI], 1.09-1.40; P < .001) and barely affects OS (hazard ratio [HR], 0.95; 95% CI, 0.90-0.99; P = .03). Conversely, upfront observation was associated with lower HGT risk in nodal (SHR, 0.71; 95% CI, 0.53-0.94; P = .01) and extranodal (SHR, 0.64; 95% CI, 0.48-0.86; P = .003) MZL and did not affect survival in extranodal disease (HR, 0.94; 95% CI, 0.97-1.02; P = .15). HGT was associated with decrease in LSS across all histologies. Upfront treatment reduced the risk of HGT only in FL but not MZL.

Reactive lymphoid hyperplasia of the liver: A rare case report

BACKGROUND: Hepatic reactive lymphoid hyperplasia (RLH) is a rare benign lymphoproliferative lesion and a poorly understood disease. It is usually asymptomatic and incidental, but it is difficult to distinguish from hepatocellular carcinoma and metastatic liver tumor on imaging, and percutaneous biopsy is not sufficient to distinguish from low-grade malignant lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), making diagnosis difficult. CASE SUMMARY: A 69-year-old woman came to our hospital for reexamination of pulmonary nodules followed by liver occupation. The lesions showed “wash-in and wash-out” on contrast-enhanced ultrasonography and magnetic resonance imaging. Enhanced magnetic resonance also showed annular envelope enhancement and limited diffusion on the ADC map during the delay period. Imaging revealed metastatic liver cancer, and the patient underwent a partial hepatectomy. However, the final histopathological diagnosis was RLH. CONCLUSION: If small isolated nodules are found in the liver of middle-aged and elderly female patients with no risk factors for liver malignancy, when the enhanced imaging suggests “wash-in and wash-out”, further focus should be placed on whether the enhanced imaging shows perinodular enhancement and whether the DWI shows limited diffusion in MRI, in order to emphasize the possibility of liver RLH diagnosis.

Correction to Staging FDG‐avidity in extranodal marginal zone lymphoma (EMZL) by disease location

Correction to Staging FDG‐avidity in extranodal marginal zone lymphoma (EMZL) by disease location

Utility of PD-1, PD-L1, and IDO-1 Stains in Ocular Extranodal Marginal Zone Lymphoma (MZL) and Diffuse Large B-cell Lymphoma (DLBCL).

Extranodal marginal zone lymphoma (EMZL) is the most common subtype of ocular lymphomas. Diffuse large B-cell lymphoma (DLBCL) and EMZL with large-cell transformation present diagnostic challenges. Radiotherapy is the standard treatment for ocular lymphomas, but complications and relapse are common. Diagnostic utility in challenging cases, as well as treatment options using immune checkpoint inhibitors, are unclear in ocular lymphomas. We herein investigated the PD-1, PD-L1, and IDO1 staining patterns in 20 cases of ocular lymphomas, including EMZL (n=14), EMZL with increased large cells (n=2), and DLBCL (n=4). PD-1, PD-L1, and IDO1 staining was not detected in lymphoma cells in any cases but was observed within the tumor microenvironment in all cases. Positivity for PD-1, PD-L1, and IDO1 in inflammatory cells was seen either intratumorally or peritumorally. In all 6 cases with significantly more large B cells, the density of PD-1, PD-L1, and IDO1 expression in the tumor microenvironment was higher than that of the remaining 14 cases without large B cells (P-value<0.0001), whereas other clinicopathologic features showed no statistical correlation. Increased expression of PD-1, PD-L1, and IDO1 in the inflammatory milieu in cases with large cells may provide diagnostic utility in small biopsies as well as therapeutic potential.

The Genetic Landscape of Primary Breast Marginal Zone Lymphoma Identifies a Mutational-driven Disease With Similarities to Ocular Adnexal Lymphoma.

Extranodal marginal zone lymphomas (eMZL) can occur in any organ and site of the body. Recent research has shown that they differ from organ to organ in terms of their mutational profile. In this study, we investigated a cohort of primary breast marginal zone lymphomas (PBMZL) to get a better insight into their morphologic and molecular profile. A cohort of 15 cases (14 female and 1 male) was characterized by immunohistochemistry (IHC) for 19 markers, fluorescence in situ hybridization (FISH), and high throughput sequencing (HTS) using a lymphoma panel comprising 172 genes. In addition, PCR for the specific detection of Borrelia spp. and metagenomics whole genome sequencing were performed for infectious agent profiling. Follicular colonization was observed in most cases, while lymphoepithelial lesions, though seen in many cases, were not striking. All 15 cases were negative for CD5, CD11c, and CD21 and positive for BCL2 and pan B-cell markers. There were no cases with BCL2, BCL10, IRF4, MALT1, or MYC translocation; only 1 had a BCL6 rearrangement. HTS highlighted TNFAIP3 (n=4), KMT2D (n=2), and SPEN (n=2) as the most frequently mutated genes. There were no Borrelia spp., and no other pathogens detected in our cohort. One patient had a clinical history of erythema chronicum migrans affecting the same breast. PBMZL is a mutation-driven disease rather than fusion-driven. It exhibits mutations in genes encoding components affecting the NF-κB pathway, chromatin modifier-encoding genes, and NOTCH pathway-related genes. Its mutational profile shares similarities with ocular adnexal and nodal MZL.

Non‑Hodgkin's lymphomas of the lacrimal sac: Current insights and future directions (Review).

Non-Hodgkin's lymphoma (NHL) of the lacrimal sac is a rare, yet clinically significant entity within the spectrum of ocular malignancies. While primary lacrimal sac lymphoma is uncommon, it poses unique diagnostic and therapeutic challenges due to its anatomical location and potential for aggressive behavior. Despite advancements being made in the current understanding and treatment of NHL, research that specifically addresses the involvement of the lacrimal sac is currently lacking. Thus, the present review aimed to provide insight into the epidemiology, clinical presentation, diagnostic modalities, histopathological features, treatment strategies and prognosis of lacrimal sac NHL. Through a methodical analysis of previous literature, the present review highlights the diverse spectrum of NHL subtypes that affect the lacrimal sac, including diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, mantle cell lymphoma and follicular lymphoma. Moreover, the present review discusses the role of advanced imaging techniques in accurate staging and treatment planning, including computed tomography (CT), magnetic resonance imaging and positron emission tomography-CT. The present review also discusses evolving treatment approaches, such as surgical intervention, chemotherapy, radiotherapy, immunotherapy, combinations of the aforementioned treatments and targeted therapy. In addition, the present review highlights the significance of multidisciplinary collaboration in attaining optimal outcomes for individuals with lacrimal sac NHL. The present review aimed to provide a basis for 'further investigations into novel treatment modalities and prognostic markers that may aid in guiding personalized management strategies, ultimately improving outcomes for patients with NHL.

Marginal zone lymphomas: a consensus practice statement from the Australasian Lymphoma Alliance.

Marginal zone lymphomas (MZLs) are a rare, indolent group of non-Hodgkin lymphomas with different diagnostic, genetic and clinical features and therapeutic implications. The most common is extranodal MZL of mucosa-associated lymphoid tissue, followed by splenic MZL and nodal MZL. Patients with MZL generally have good outcomes with long survival rates but frequently have a relapsing/remitting course requiring several lines of therapy. The heterogeneous presentation and relapsing course present the clinician with several diagnostic and therapeutic challenges. This position statement presents evidence-based recommendations in the setting of Australia and New Zealand.

Indolent nonprogressive multifocal choroidal lymphoid lesions with late development of systemic lymphoma

Purpose: To report a case of indolent nonprogressive multifocal choroidal lymphoid lesions with late development of pulmonary low-grade B-cell lymphoma after lymphoid lesion regression. Methods: Case report. Results: A 79-year-old male was followed with ocular and systemic surveillance over a sixteen-year period for unilateral nonprogressive choroidal lesions presumed to be a benign lymphocytic disease of the choroid. Workups for systemic lymphoma and birdshot chorioretinopathy were negative. After sixteen years of observation, the choroidal lesions had largely regressed. Recent diagnosis of atrial fibrillation led to an incidental discovery of a right lower lobe lung lesion measuring 4.5 cm. Computerized tomography-guided biopsy showed low-grade B-cell lymphoma. There was no additional systemic disease detected. The patient underwent right lower lobectomy revealing extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Conclusion: Patients with indolent nonprogressive multifocal choroidal lymphoid lesions should be monitored regularly for late systemic disease, which although rare, can develop even after years of follow-up.

Chinese expert consensus on the diagnosis and management of ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma (2023 edition)

Ocular adnexal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML) is a common malignant tumor that affects the ocular adnexal region. The incidence of OAML is increasing due to the aging population. The tumor invades the ocular adnexal region, which can result in abnormal ocular appearance and function, thereby reducing the quality of life. Currently, there is no standardized diagnosis and management guideline for OAML. To enhance the standardization of diagnosis and management in OAML, a collaborative effort was undertaken by esteemed organizations in China. The Cellular Immune Therapy Committee of China Association for Promotion of Health Science and Technology, the Ocular Tumor Committee of Chinese Medical Doctor Association for Ophthalmologist Branch, the Imaging Medicine Branch of Chinese International Exchange and Promotion Association for Medical and Healthcare, the Tumor and Microecology Professional Committee of China Anti-cancer Association, and the Lymphoma Immunotherapy Committee of Beijing Cancer Prevention Society jointly convened a panel of experts to develop the inaugural "Chinese Expert Consensus on the Diagnosis and Management of ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma (2023 edition)"..

The paraneurium and the tumefactive appearance of peripheral nerve neurolymphomatosis: illustrative case.

Peripheral neurolymphomatosis (NL) is an often-misdiagnosed condition characterized by lymphomatous infiltration within the peripheral nerves. Its rarity and complexity frequently result in delayed diagnosis and suboptimal patient outcomes. This study aims to elucidate the role of the paraneurium (circumneurium) in NL, emphasizing its diagnostic and therapeutic significance. A 72-year-old man presented with lesions on his right lower eyelid. Initial diagnostics were inconclusive until an excisional biopsy confirmed extranodal marginal zone lymphoma. Following a complete metabolic response to rituximab treatment, the patient relapsed 14 months later with progressive lymphoma and bilateral sciatic nerve involvement, as confirmed by positron emission tomography-computed tomography and magnetic resonance imaging. This paper underscores the critical role of the paraneurium in NL, enhancing understanding of its pathophysiology. Integrating advanced imaging techniques have proved essential in accurately identifying neurolymphomatous involvement within the paraneurium. This study paves the way for more effective management strategies in NL and similar conditions, focusing on improving patient care and outcomes.

Transformation risk and associated survival outcome of marginal zone lymphoma: A nationwide study.

Histological transformation into an aggressive B-cell lymphoma indicates a poor survival outcome for patients with indolent marginal zone lymphoma (MZL), which has been less studied. Large-scale data with long-term follow-up to investigate MZL transformation is limited. Here, by reporting a US-Nationwide cohort of 30,619 MZL patients diagnosed between 2000 and 2019, we found that transformation occurred in 2.08% (N = 624) of MZL cases, with the transformation incidence of 3.1 per 1,000 person-years. Advanced Ann Arbor stage, nodal MZL (NMZL) and splenic MZL (SMZL) were associated with an elevated risk of transformation. Certain subtype-specific characteristics, such as non-gastric extra-nodal MZL (vs. gastric, HR, 1.51, 95%CI 1.13-2.04; p = 0.006), and receiving splenectomy for SMZL (HR, 2.04, 95%CI 1.28-3.26; p = 0.003), also indicated a higher risk of transformation. Besides, transformation independently increased the overall mortality risk (HR, 1.38, 95%CI 1.24-1.53, p < 0.001), especially the higher lymphoma-caused mortality risk (HR, 3.21, 95%CI 2.81-3.67, p < 0.001). Transformation was also associated with a higher percentage of lymphoma-caused deaths. The post-transformation prognostic analyses demonstrated that female gender and age ≥ 65 years independently affected patients' mortalities. These findings, based on the largest cohort to date, contribute to a better understanding of transformed MZL, and provide valuable reference points for guidelines and patient counseling.

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.