Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

Primary lymphoma of the uterine cervix: a clinicopathologic study of 13 cases with review of additional 54 cases in the literature.

Primary lymphoma of the uterine cervix (LUCX) is extremely rare, and its diagnosis is challenging. However, its clinicopathological features have not been well characterized. Thirteen primary LUCX patients were retrospectively studied, and 54 patients from the literature were reviewed. Primary LUCX was identified in 0.22% (13/6000) of patients with uterine cervical malignancies in our institution. The patients' median age was 51years (range: 22-85years). All patients had a bulk of neoplasms in the uterine cervix. The median tumour diameter was 6cm (range: 1.5-10cm). Approximately 78.0% (39/50) of the patients initially presented with irregular vaginal bleeding or discharge. Moreover, 86.7% (39/45) had Ann Arbor stage I or II. Diffuse large B-cell lymphoma, not otherwise specified, was the most common type, accounting for 85.0% (57/67) of primary LUCX cases. Follicular lymphoma (7.5%, 5/67), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (4.5%, 3/67), mantle cell lymphoma (MCL), blastoid variant (1.5%, 1/67), and peripheral T-cell lymphoma (1.5%, 1/67) were occasionally observed. Three patients (7.1%, 3/42) with DLBCL, NOS died from the disease during the follow-up period. Their 5-year overall survival (OS) rate was 93.5%. The patient with MCL, blastoid variant in our present cohort died of the disease 33months after diagnosis. Primary LUCX is an extremely rare condition. The clinical symptoms are non-specific. DLBCL, NOS is the most common histologic type, showing a favourable outcome with accurate diagnosis and timely and optimal treatment.

Alpha Heavy Chain Disease Post-Diffuse Large B-cell Lymphoma Remission: A Series of Two Cases

Abstract Introduction/Objective Heavy chain disease is the production of abnormal monoclonal immunoglobulin heavy chains. Alpha heavy chain disease is typically identified in mucosa-associated lymphoid tissue lymphomas and is secreted due to chronic infection. The alpha heavy chain can manifest as hypogammaglobulinemia or a normal serum protein electrophoresis (SPEP). Broadband may appear in the alpha-2 or beta mobility regions. Methods/Case Report We describe two cases in which a monoclonal alpha heavy chain was detected in a 60-year-old female with diffuse large B-cell lymphoma (DLBCL) of the thoracic spine and a 71-year-old female with mediastinal DLBCL. Both patients achieved clinical and radiological remission. Results (if a Case Study enter NA) A distinct IgA band without an associated light chain was detected on the first patient's serum immunofixation essay (SIFE) one year later. For the second case, there was a distortion of the beta-2 region, elevated kappa free light chain (230.6 mg/dL), and a kappa to lambda free light chain ratio of 14.23, suggesting alpha heavy chain disease and a possible monoclonal gammopathy of unknown significance. Interestingly, even with a monoclonal IgA, the patients remained symptom-free, without any gastrointestinal manifestations, and concurrent PET scans show no recurrence. Conclusion To the best of our knowledge, these are the first two cases describing the presence of alpha heavy chain disease in association with DLBCL. The significance of alpha heavy chain secretion in patients with a history of DLBCL needs to be further assessed and we need to identify the possible presence of a non-clonally related paraprotein post-treatment for DLBCL.

Gastrointestinal Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma with Synchronous Precancerous/Malignant Epithelial Mucosal Lesions: A Clinico-Pathologic Review

Abstract Introduction/Objective Mucosa-associated lymphoid tissue (MALT) lymphoma of the gastrointestinal(GI) tract and synchronous precancerous/malignant epithelial lesions have been sporadically reported in literature. We sought to assess the incidence of GI MALT lymphoma and synchronous epithelial lesions. Methods/Case Report We performed a retrospective study by searching the pathology files at our institution from 1992 to December 2021, for GI lymphomas including extranodal marginal zone lymphoma(E-MZL). Results (if a Case Study enter NA) There were a total of 178 cases of lymphoma involving the GI tract. The basis of this report was formed by the 40/178(22.5%) cases, which were E-MZL. Twenty-four were males and 16 females(age range:37-80 years; mean:62 years). Sites of tumors were stomach(21), colon(6), ileum(4), duodenum(4), rectum(3), and cecum(2). Four cases were multifocal. Lymph nodes were assessed in 8/40, of which 4 were positive. One patient had malignant pleural effusion and another had retroperitoneal soft-tissue involvement. Overall, 11/40(27.5%) cases had a synchronous precancerous/malignant epithelial lesion. Gastric E-MZL were the most common (21), out of which 8(38%) were associated with synchronous epithelial lesion (3 gastric adenocarcinomas and 5 tubular adenomas(TA) at different colorectal locations). Out of 6 colonic E-MZL, 2 were associated with synchronous TAs at different colorectal sites and one rectal E-MZL was associated with cecal TA. Conclusion In our cohort, precancerous/malignant epithelial lesions were seen in 11/40(26.8%) of GI E-MZL cases. Gastric adenocarcinomas comprised 3/8 (37.5%) of gastric synchronous precancerous/malignant epithelial lesions; the association of E-MZL and gastric adenocarcinoma is well-known, arising in the background of chronic atrophic gastritis and intestinal metaplasia secondary to chronic inflammatory disorders. The remaining 8 cases of synchronous mucosal epithelial lesions were TAs at different colorectal sites. Based on our observations, unlike gastric adenocarcinoma, the association of colorectal pre-cancerous lesions with E-MZL is less likely, since, in all cases, the TAs were seen in sites other than E-ZML sites and also, sporadic colorectal TAs are a common pathology. However, possible association between E-MZL and precancerous mucosal epithelial lesions needs more work and further investigation.

First-line antibiotic treatment in patients with localized extragastric mucosa-associated lymphoid tissue lymphoma.

Between January 2010 and December 2015, we enrolled 28 patients with stage IEI/IIE1 extragastric mucosa-associated lymphoid tissue (MALT) lymphoma who received first-line antibiotic treatment, after informing them about the pros and cons of alternative therapies. In addition, during the same period, 64 patients with stage IE/IIE1 disease who received conventional treatment were selected as the control group. The most common primary sites were the ocular adnexal area (17 cases), followed by the salivary glands (four cases), pulmonary (three cases), and thyroid, trachea, larynx, and colon region (one case each). First-line antibiotic treatment resulted in an overall response rate of 57.1%: 12 patients achieved complete remission (CR), while four achieved partial remission (antibiotic-responsive tumors). Monoclonal gammopathy was significantly prevalent in antibiotic-unresponsive tumors than in antibiotic-responsive tumors (50.0% [6/12] vs. 12.5% [2/16], p=0.044). After a median follow-up of 7years, all patients with CR remained lymphoma-free, with 7-year event-free survival (EFS) and overall survival (OS) rates of 62.7% and 96.4%, respectively. The 7-year EFS and OS rates of patients who received conventional treatments were 73.1% and 91.1%, respectively. Compared with that noted in patients who received conventional treatment, antibiotic treatment was effective in some patients with localized extragastric MALT lymphoma.

PSAT295 Low Grade B-CELL Lymphoma and Follicular Cancer in a Patient with Hashimoto's Thyroiditis Presenting as Two Different Thyroid Nodules

Abstract We present an 88 year old female with a history of hypothyroidism due to Hashimoto's thyroiditis who noted a lump in the left side of her neck. Thyroid ultrasound revealed multiple nodules throughout the thyroid gland. The right lobe contained a 4.3 cm solid, dominant nodule and the left lobe contained a 4.2 cm lobulated hyperechoic nodule. Ultrasound-guided fine-needle aspiration biopsy of the 4.3 cm right thyroid nodule revealed follicular lesion of undetermined significance with predominantly Hurthle cells. Thyroseq was positive for aTERT and EIF1AX mutations. Ultrasound-guided fine-needle aspiration biopsy of the 4.2 cm left thyroid nodule revealed malignant cells consistent with a low-grade B-cell lymphoma. She underwent a total thyroidectomy. The final pathology report revealed both a 5.5 cm follicular carcinoma in the right lobe and a low-grade B-cell lymphoma most compatible with extra nodal marginal zone lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma) involving predominantly the left lobe of the thyroid. She is beginning radiation treatment for the lymphoma. Three months after radiation treatment is completed, she will undergo radioactive iodine treatment for the follicular carcinoma. Thyroid cancer is the most common endocrine malignancy. However, the thyroid is an uncommon site of cancer overall, accounting for only 1.5% to 4.7% of new cancer cases in the general population of the United States. Malignant lymphoma presenting as a primary neoplasm in the thyroid is even more uncommon and represents only 1 to 5% of all thyroid malignancies. Hashimoto's thyroiditis is a known risk factor for MALT lymphoma. However, there is no known association between Hashimoto's thyroiditis and follicular carcinoma. There are several reports of patients with presence of both papillary thyroid cancer and MALT lymphoma. One case was reported of simultaneous MALT lymphoma and medullary thyroid cancer. This is the first case of a patient with both follicular thyroid cancer and MALT lymphoma in the thyroid gland. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT289 Extranodal Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT) Type of the Thyroid: A Rare Tumor That Requires a Second Look

Abstract Background Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type of the thyroid, or MALT lymphoma of the thyroid, is a rare, indolent tumor that accounts for only 1-2% of extranodal lymphomas. It is often associated with lymphocytic thyroiditis - a benign condition that might not be given additional investigation. Clinical case A 79-year-old male consulted due to a 3-year history of a gradually enlarging, painless anterior neck mass accompanied by hoarseness. He denied fever, weight loss, dysphagia, dyspnea, palpitations, heat or cold intolerance, or changes in bowel movement. On physical exam, a 4×3×1 cm firm, fixed, non-tender right anterior neck mass and a 2×2 cm right supraclavicular mass were palpated. Thyroid function tests showed: TSH 3.301 uIU/mL (0.55 - 4.78 uIU/ml), FT3 2.560 pg/mL (2.30 - 4.20 pg/mL) and FT4 0.720 ng/dL (0.89 - 1.76 ng/dL). Neck ultrasound revealed multiple cervical lymph nodes measuring 1-2 cm in the right anterior, posterior, submandibular, and left submandibular areas. A lobulated heterogeneous mass measuring 9.7×2.9×4.3 cm occupied almost the entire right thyroid lobe, with intralesional and peripheral vascularity. The left thyroid lobe had an irregular, solid, isoechoic nodule measuring 0.9×0.5×0.9 cm. Fine needle aspiration biopsy of the right thyroid mass showed lymphocytic thyroiditis (Bethesda category II). The patient underwent total thyroidectomy with frozen section and selective neck dissection on the right (levels II, III, IV, and V). Final histopathology and immunohistochemical stains revealed extranodal marginal zone lymphoma of the thyroid gland, with high grade transformation to diffuse large B-cell lymphoma in 10% of the tumor. Level II, III and V lymph nodes were positive for marginal zone lymphoma. Histopathology also showed an adenomatous goiter with lymphocytic thyroiditis. The patient was started on levothyroxine 75 mcg once daily. He completed 1 cycle of chemotherapy (R-CHOP). Two weeks after chemotherapy, he developed febrile neutropenia and expired due to sepsis. Conclusion In thyroid nodules and masses where lymphocytic thyroiditis is identified on fine needle aspiration biopsy, particularly in large masses accompanied by cervical lymphadenopathy, the possibility of an existing MALT lymphoma of the thyroid should be considered, and further investigation may be warranted. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT288 Mucosa-associated Lymphoid Tissue Thyroid Lymphoma Presenting as a Rapidly Growing Neck Mass in an Asymptomatic Male Patient

Abstract A 77-year-old male was referred to endocrinology for a 2-month history of a rapidly enlarging painless left neck mass. His only other complaint was unintentional weight loss of 10 pounds over 12-months. On exam patient had a firm, smooth, nontender 2 cm thyroid/neck mass extending below left clavicle. No abnormalities were detected for right thyroid gland. There was no palpable lymphadenopathies or hepatosplenomegaly noted. No signs of tracheal, esophageal, or neck vein compression were noted. He did not have any history of radiation exposure, family history of thyroid-related disorders, or malignancy. Laboratory test including complete blood count, comprehensive metabolic profile and TSH were within normal limits. TPO antibody was positive. Ultrasound revealed a 7.7×4.1×4 cm hypoechoic spongiform mass replacing the left lobe of the thyroid, as well as scattered sub centimeter nodules. Contrasted CT of the neck confirmed 6.5×5.2×3.9 cm left thyroid mass causing mild rightward deviation of the trachea and extending into the superior mediastinum and no lymphadenopathy. FNA of the mass revealed presence of crushed lymphoid cells without thyroid follicular cells, which raised the possibility of chronic lymphocytic thyroiditis. FDG- PET scan showed intense, heterogeneous FDG uptake in the left neck mass (max SUV=10.7), likely arising from the left thyroid lobe concerning for thyroid malignancy without evidence of distant metastases. The patient underwent a left thyroid nodule core biopsy with subsequent left thyroid hemithyroidectomy. The pathology stains of the excised left thyroid lobe core biopsy showed extra nodal zone lymphoma of mucosa- associated lymphoid tissue (MALT Lymphoma) with extensive plasmocytic differentiation. Surgical path confirmed extra nodal zone lymphoma of mucosa-associated lymphoid tissue (MALT Lymphoma) with extensive plasmocytic differentiation and foci of chronic lymphocytic thyroiditis. Immunochemistry studies supported a diagnosis of plasma cell neoplasm or the plasma cell component of a B-cell lymphoproliferative disorder. Short-term follow-up FDG-PET and CT imaging demonstrated post-surgical changes without evidence of recurrence. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

The Impregnated Integument- Cutaneous Marginal Zone Lymphoma

Primary cutaneous marginal zone B cell lymphoma (CMZL) is an indolent lymphoma demonstrating nonspecific post-germinal centre B cell phenotype. The B cell lymphoma is derived from mature, predominantly post-germinal centre B lymphocytes. World Health Organization (WHO) classifies the cutaneous B cell lymphoma as an extra-nodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT).

ODP333 Mucosal-Associated Lymphoid Tissue Lymphoma: a Rare Condition in the Differential Diagnosis of a Parasellar Mass

Abstract The differential diagnosis for sellar and parasellar masses is broad and includes pituitary tumors, inflammatory lesions, meningioma, and lymphoma. In rare cases, the latter can manifest as extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT)-subtype. We report a case of MALT-lymphoma presenting as a parasellar mass. A 68-year-old woman presented with several months of diplopia, cognitive slowing, and progressive balance issues. Brain MRI revealed a 4.6×2.3×1. 0 cm dural skull-based lesion extending from the left tentorium cerebelli to the left cavernous sinus and sella with mass effect on the optic chiasm and pituitary gland. Hormonal assessment revealed elevated prolactin at 93 ng/mL (NR 2.8-29.2) thought to be due to stalk effect. There were no abnormalities in other axes. CSF analysis demonstrated elevated protein (211 mg/dL, NR 15-45) and was negative for malignant cells. Due to the degree of cavernous sinus involvement, the mass was deemed surgically unresectable. Her PCP started dexamethasone 10mg daily for her neurologic symptoms, resulting in subsequent symptomatic improvement, reduction in mass size, and normalization of prolactin. However, she experienced weight gain, glucose intolerance, and fatigue, so dexamethasone was tapered and stopped after a 5-month course. Nine months later, she re-presented with symptoms of a sixth cranial nerve palsy. MRI demonstrated interval increase in mass size, protrusion into the left sella, and possible upward displacement of the pituitary. No pituitary hormone deficiencies were noted. Tumor biopsy and debulking revealed MALT-lymphoma. She received external beam radiation (200 cGy/fraction for 12 fractions) with improvement in symptoms and size of the mass. A PET-CT showed no evidence of other FDG-avid lesions. Follow-up MRI showed resolution of the mass with only minimal thickening along the left cavernous sinus. She continues to follow with Endocrinology post-radiation therapy for hormonal monitoring. Her pituitary axes have remained intact for 7 years. Steroid-responsive sellar and parasellar masses often invoke associations with inflammatory conditions such as sarcoidosis and idiopathic hypertrophic pachymeningitis. Lymphoma, and in particular MALT-lymphoma, also need to be considered in the differential diagnosis for these lesions. MALT-lymphomas of the central nervous system (CNS) tend to occur in women and arise from the dura. In one retrospective analysis, about 50% of cases occurred as primary lymphoma in the CNS while the remaining had systemic disease. Ten out of 13 subjects (77%) in a case series of primary CNS MALT-lymphoma had a complete response to surgery, chemotherapy, and/or radiation therapy. In a separate retrospective analysis, 3 out of 70 subjects (4.3%) experienced a recurrence over a median follow-up of 23 months after treatment. Given the importance of radiation therapy to the management of these tumors, Endocrinologic follow-up is essential given the increased risk of hypopituitarism after intracranial radiation. Presentation: No date and time listed

Histopathological Features of Helicobacter pylori Infection in Gastric Mucosa.

To investigate the histopathological characteristics of Helicobacter pylori (Hp) infection in the gastric mucosa in the process from occurrence to intraepithelial neoplasia. Specimens obtained from the endoscopic biopsy and endoscopic submucosal dissection of 2457 cases of gastric Hp infection were observed and assessed in detail using histology and immunohistochemistry techniques. The condition was divided according to the histopathological characteristics of gastric mucosal damage caused by Hp infection. The histopathological characteristics and immunophenotype of each stage were subsequently elucidated. Helicobacter pylori is initially implanted in the mucus layer covered by the epithelium on the surface of the gastric mucosa. It then selectively adheres to the cytoplasm of the surface mucus cells, which makes the oval and spherical particles containing mucus that is wrapped by the bounded membrane in the cytoplasm on the nucleus of the surface mucus cells disappear, while the cytoplasm undergoes spiderweb-like vacuolar degeneration. This leads to the proliferation and transformation of the surface mucous cells before developing into intraepithelial neoplasia. In the process of histomorphology, mucosal ulcers, mucosal lymphoid tissue proliferation, gland atrophy, intestinal epithelial metaplasia, mucosa-associated lymphoid tissue lymphoma, and adenocarcinoma may occur. In this study, the condition was divided into five stages according to the histopathological characteristics of gastric mucosal damage caused by Hp infection, as well as the degree of gastric mucosal damage and involvement depth as follows: the mucus infection stage, the surface epithelial cell infection stage, the lamina propria lesion stage, the mucosal atrophy stage, and the intraepithelial neoplasia stage. Understanding the histopathological characteristics of gastric Hp infection in terms of its occurrence and development into intraepithelial neoplasia is conducive to the precise treatment and tracking of malignant cell transformation, and is of great significance in controlling the occurrence and development of gastric cancer.

Blood MALT1 deficiency is common and relates to unfavorable induction therapy response and survival profile in acute myeloid leukemia patients

ABSTRACT Background Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) regulates T helper/regulatory T cell balance, autoimmunity development, and leukemia pathogenesis. As a result, this study aimed to investigate the clinical role of MALT1 in patients with acute myeloid leukemia (AML). Methods MALT1 expressions were measured in peripheral blood mononuclear cell (PBMC) from 90 newly diagnosed AML patients before and after induction treatment using RT-qPCR. Moreover, MALT1 expressions were also determined in 50 disease controls (DCs) and 50 healthy controls (HCs). Results MALT1 expression was reduced in AML patients compared to HCs and DCs (both adjusted P < .001). Lower MALT1 expression was related to white blood cells >10×109/L (P = .037) and poor risk stratification (P = .020) in AML patients. MALT1 expression was elevated during induction treatment not only in total AML patients (P < .001), but also in subgroups of patients achieving complete remission (CR) (P < .001) and in those not achieving CR (P = .001). Furthermore, MALT1 expressions before induction treatment (P = .042) and after induction treatment (P < .001) were both increased in AML patients with CR compared to those with non-CR. Interestingly, both pre- and post-treatment MALT1 low (vs. high) were related to shorter accumulating event-free survival (EFS), which was also associated with a reduced accumulating overall survival (OS) (all P < .05). Furthermore, MALT1 increment during induction treatment < 50% was related to unsatisfied accumulating EFS (P = .001) and OS (P = .007). Conclusion PBMC MALT1 deficiency is common and relates to unfavorable induction therapy response and survival profile in AML patients.

Persistent Stomach Pain In The young Age Patient: A Case Of Primary Gastric Burkitt's Lymphoma

Lymphoma is the second most common gastric cancer, following gastric adenocarcinoma. Most gastric lymphomas are mucosa-associated lymphoid tissue lymphomas or diffuse large B-cell lymphomas. Primary gastric Burkitt’s lymphoma is a subtype of non-Hodgkin lymphoma and represents an aggressive and rare malignity with the fewest cases reported globally. Primary gastrointestinal non-Hodgkin lymphoma is a rare condition. Burkitt’s lymphoma is an aggressive form of B-cell lymphoma endemic to Africa while it is not endemic to the rest of the world. Here we presented a young immunocompetent male patient who had weight loss and was admitted with a stomachache. Upper gastrointestinal endoscopy and biopsy detected a large primary gastric Burkitt’s lymphoma. While long-term survival rates are possible with early diagnosis and timely appropriate treatment, delay in treatment can be fatal for such patients.

Primary MALT lymphoma of thyroid with hypothyroidism and absence of Hashimoto’s disease

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Response Adapted Ultra Low Dose Radiation Therapy for the Definitive Management of Orbital Indolent B-Cell Lymphoma

<h3>Purpose/Objective(s)</h3> Radiation therapy (RT) to doses of 24-30 Gy is used for the treatment of indolent B-cell lymphoma (BCL); however, significant acute and late ocular effects are common. We aimed to develop a response adapted (RA) strategy that maintains excellent disease outcomes but reduces orbital morbidity. <h3>Materials/Methods</h3> We performed a phase II prospective study of a RA strategy in 50 patients (pts) with stage I-IV orbital indolent BCL. Pts were treated with ultra-low dose (ULD) RT to 4 Gy in 2 fractions and assessed in 3-month intervals for response. Pts with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions. Pts that had a complete response (CR) to ULD RT were observed. We also evaluated this treatment strategy in a separate 55 pt retrospective cohort. <h3>Results</h3> From July 2015-January 2021 51 pts were enrolled. Fifty evaluable pts had follow-up for study inclusion. The median age was 63 years (29-88); 62% were female (n=31). Pts had MALT lymphoma (n=32, 64%), follicular lymphoma (FL, n=16, 32%) and low grade BCL (n=6, 12%). Most pts (62%, n=31) had stage I disease limited to one (n=28) or both (n=3) orbits. Pts had newly diagnosed (n=36, 72%); relapsed (n=9, 18%) and refractory lymphoma (n=5, 10%). At a median follow up of 35 months [95% CI 22.2 – 37.4], 90% of pts (n=45) experienced a CR to RA RT, including 44 pts that had a CR to ULD RT (median time to CR 3.4 months) and 1 pt that had a CR after an additional 20 Gy. No local recurrences were observed. Treatment was well tolerated with no grade ≥3 toxicity. Five pts did not have a CR to planned RA therapy including 1 pt that refused additional RT, one pt treated with rituximab, one pt that had a PR on initial evaluation but has not returned for subsequent in person evaluations due to COVID, one pt being observed with stable disease and a final pt that received an additional 20 Gy to the orbit that has a persistent stable mass after the 20 Gy. In a planned subset analysis of 26 pts with newly diagnosed stage 1 disease (MALT, n=22; FL, n=3; low grade BCL, n=1); 92.3% (n=24) had a CR to RA RT, with one pt requiring an additional 20 Gy. For all 26 pts with newly diagnosed stage 1 disease, the 3-year freedom from distant relapse rate was 90.4% with 3 distant relapses (contralateral orbit, n=2; paratracheal nodes, n=1). The median follow-up among the 55 pts (MALT, n=38; FL, n=13; low grade B-cell lymphoma, n=4) treated in the retrospective cohort between March 2013 and October 2021 was 28.7 months (95% CI 21.2 - 36.1); 98% (n=54) of pts had a CR with RA RT, including 2 pts with a CR after an additional 20 Gy. The remaining pt went on to receive systemic therapy in lieu of additional RT for persistent disease. Among the 54 pts that had a CR with RA RT there was one local relapse in a pt with conjunctival FL 27.8 months after experiencing a CR to ULD RT. This pt received 20 Gy with resolution of the locally relapsed disease. <h3>Conclusion</h3> We observed excellent disease control with negligible toxicity in the first prospective study assessing this novel approach of RA ULD RT for pts with indolent B-cell lymphoma.

Risk of Diabetes Mellitus after Radiotherapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

<h3>Purpose/Objective(s)</h3> The long-term effect of radiation on pancreas has been mostly studied for pediatric patients with the lack of individual radiation dosimetric data. The purpose of this study was to investigate the effect of radiotherapy (RT) on the risk of newly developed diabetes mellitus (DM) in patients with gastric mucosa-associated lymphoid tissue lymphoma (GML) using individual radiation dosimetric analysis. <h3>Materials/Methods</h3> We retrospectively reviewed 225 patients without history of DM who received curative aim treatment for stage IE GML between August 2007 and June 2020. Involved site RT to the whole stomach was delivered in 83 patients (36.9%). The pancreas was delineated in each patient's computerized tomography scan for dosimetric analysis. <h3>Results</h3> At a median follow-up time of 49.0 months (range, 3.0-155.3 months), the 3-year cumulative incidence of DM was 3.9% in all patients, and 7.9% and 1.6% in patients who received and did not receive RT, respectively (p=0.009). The mean pancreatic dose (D_mean) was independently associated with DM (p=0.027). As a result of recursive partitioning analysis, patients were classified into low (D_mean <21 Gy), intermediate (D_mean ≥21 Gy and BMI <27.0kg/m²), and high-risk groups (D_mean ≥21 Gy and BMI ≥27.0kg/m²) with 5-year DM incidence of 1.5%, 6.3%, and 54.3%, respectively (p<0.001). <h3>Conclusion</h3> Our results indicate that incidental irradiation to the pancreas can increase the risk of DM, which was dependent on pancreas D_mean. In addition, not only reducing pancreas D_mean but also controlling BMI may need to be combined to effectively prevent DM after RT.

Novel Insights into Pathophysiology of Orbital Inflammatory Diseases and Progression to Orbital Lymphoma by Pathway Enrichment Analysis.

Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are currently treated with non-specific immunosuppressive agents based on non-randomized, uncontrolled studies. Therefore, relapses and prolongated courses are common and remain challenging. For a more specific therapy, a better understanding of the underlying pathophysiology is crucial. Therefore, we aimed to analyze signaling pathways to expand the knowledge on the pathophysiology and possibly identify specific targets in the future, as occurred recently in Graves’ orbitopathy with the IGF-1 receptor. Furthermore, we analyzed potential mechanisms for the described potential progression to orbital MALT (mucosa-associated lymphoid tissue) lymphoma. The investigation cohort for this screening study comprised of 12 patients with either typical NSOI (n = 6), IgG4-ROD or MALT lymphoma (n = 3 each). Mean age was 56.4 ± 17 years. MALT samples, in contrast with IgG4-ROD and NSOI, showed overall upregulation for extracellular matrix receptor interaction (ECM) and adipocytokine signaling. Investigating signaling compounds for MALT samples, differentially expressed genes were re-identified as targets with relevant expression. Even though pathway analysis showed differentially altered products when comparing IgG4-ROD with MALT, main conductors of differentiation in B- and T-cell signaling were commonly altered when observing the microenvironment of examined tissues. Our data reveal the characteristic differences and similarities in genetic-expression-based pathway profiles between MALT lymphoma, IgG4-ROD and NSOI, which may be useful for elucidating the associated pathogenic mechanisms and developing specific treatments for these orbital diseases.

Predisposing Factors, Clinical Picture, and Outcome of B-Cell Non-Hodgkin’s Lymphoma in Sjögren’s Syndrome

Among other systemic autoimmune diseases, primary Sjögren syndrome (pSS) bears the highest risk for lymphoma development. In pSS, chronic antigenic stimulation gradually drives the evolution from polyclonal B-cell expansion to oligoclonal/monoclonal B-cell predominance to malignant B-cell transformation. Thus, most pSS-related lymphomas are B-cell non-Hodgkin lymphomas (NHLs), with mucosa-associated lymphoid tissue (MALT) lymphomas predominating, followed by diffuse large B-cell lymphomas (DLBCLs) and nodal marginal zone lymphomas (NMZLs). Since lymphomagenesis is one of the most serious complications of pSS, affecting patients’ survival, a plethora of possible predisposing factors has been studied over the years, ranging from classical clinical, serological, hematological, and histological, to the more recently proposed genetic and molecular, allowing clinicians to timely detect and to closely follow-up the subgroup of pSS patients with increased risk for lymphoma development. Overall predisposing factors for pSS-related lymphomagenesis reflect the status of B-cell hyperactivity. Different clinical features have been described for each of the distinct pSS-related B-cell NHL subtypes. While generally pSS patients developing B-cell NHLs display a fairly good prognosis, outcomes in terms of treatment response and survival rates seem to differ depending on the lymphoma subtype, with MALT lymphomas being characterized by a rather indolent course and DLBCLs gravely affecting patients’ survival.

Lacrimal sac lymphoma: a case series and literature review

To study the clinical and pathological characteristics of the lacrimal sac lymphoma, which is rare but it is the major type of non-epithelial malignant tumor in the lacrimal sac region. Sixty-four cases of malignant lacrimal sac tumors in our hospital from 1986 to 2020 were retrospectively reviewed. Eight cases of lacrimal sac lymphoma were carefully reviewed. There were five mucosal-associated lymphoid tissue (MALT) lymphomas, one diffused large B-cell lymphoma, one NK/T cell lymphoma, and one mantle cell lymphoma. All eight patients represented symptoms of epiphora with swelling in the lacrimal sac for a certain period of time and showed no signs of systemic involvement at the first time of clinical visits. They had received either chemotherapy or radiotherapy after surgery. Long-term follow-up (from 11 to 220mo) showed that, except one patient with MALT lymphoma died for unknown reasons at 104mo after surgery, the other 7 patients were all alive with no signs of local recurrence, neither in other organs. Non-epithelial malignant tumors of the lacrimal sac are rare and lymphoma is the major subtype.

Analysis of Helicobacter pylori in Saliva of Patients with Laryngopharyngeal Reflux and Non-Laryngopharyngeal Reflux

BACKGROUND : Helicobacter pylori is a gram-negative bacteria known as the causative agent of chronic gastritis, peptic ulcer, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Several studies have correlated H. pylori in the pathogenesis of upper airway diseases. H. pylori can be detected in saliva, oropharyngeal aphthae, nasal and sinus mucosa, secretions from the tympanic cavities, larynx, and pharyngeal lymphoid tissue. The diagnosis of LPR can be made simply by examining saliva.&#x0D; AIM : The aim of the study is to analyze the presence of H.pylori in the saliva of LPR and non LPR patients.&#x0D; METHODS : This study is an analytic observational study with a case control design. The research was conducted in the ENT-KL Department of Dr. M. Djamil Hospital, Padang, Indonesia. PCR examination was carried out at the Biomedical Laboratory of the Faculty of Medicine, Andalas University on saliva samples to detect the presence of H.Pylori. The study was conducted on 22 LPR patients and 22 control subjects.&#x0D; RESULT : LPR patients are more common in women than men, which were 12 women and 10 men. The average age of LPR patients is 43.7 years. The presence of H.pylori in LPR patients was 86.4%, while in the non-LPR group was 50%. After being tested using the Chi-square test, a significant difference was found between the presence of H. Pylori and the incidence of LPR (P = 0.010).&#x0D; CONCLUSION : There was an increase in the frequency of the presence of Helicobacter Pylori in patients with LPR compared to Non LPR patients after statistical analysis.&#x0D;

Local recurrence as extraocular muscle lymphoma after 6 years of chronic myositis: a case report

BackgroundExtraocular muscle is usually affected by thyroid disease or inflammatory pseudotumor, but seldom by neoplastic process. Primary malignant lymphoma involving isolated extraocular muscle is very rare, especially after 6 years of chronic myositis.Case presentationA middle-aged female presented with swelling of the lower lid of the right eye for 2 months. Magnetic resonance imaging showed significant enlargement of the right inferior rectus muscle belly. The patient first presented 6 years prior with upper eyelid swelling. A total of 5 surgical biopsies of the right eye were performed during 6 years with the following successive findings: inflammatory pseudotumor, chronic inflammation, inflammatory lesions, IgG4-related ophthalmic disease, and lastly, extraocular muscle extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).ConclusionMALT lymphoma may have occurred as a result of chronic extraocular myositis. Malignancy should be considered in patients with recurrent painless extraocular muscle hypertrophy. Differential diagnosis can rule out thyroid-associated ophthalmopathy (TAO), whose symptoms are similar. Diagnosis confirmation by biopsy is warranted if necessary.