Thyroid lymphoma: A single institution’s experience

18533 Background: Extranodal lymphomas account for a significant proportion of non-Hodgkin’s lymphomas. Thyroid lymphoma accounts for <2% of these. Lymphoma represents approximately 2% of all malignant thyroid tumours and is almost always of B-cell lineage. The main presenting symptom is a rapidly enlarging goiter and approximately half present with disease limited to the thyroid gland, designated stage IE. Due to its rarity, there is limited information with regard to prognosis or management. Pre-existing chronic autoimmune (Hashimoto’s) thyroiditis is the only known risk factor. Methods: We retrospectively reviewed all cases of thyroid lymphoma found in our institution over a 15 year period (1985–2000). Eleven patients were identified as suitable for analysis. Diagnosis and staging involved a full history and physical examination with relevant serology. Radiological imaging included computerized tomography, plain radiographs and ultrasound. Bone marrow aspirate and biopsy were performed in ten of the patients and patients were then staged according to the Ann Arbour Classification. We specifically analysed patients for their epidemiological features, presentation, treatment and their overall outcome. We compared our data to those from earlier series. Results: Seven of the 11 patients were female with a median age of diagnosis of 56. Most patients complained of neck swelling for a number of months but dysphagia, dyspnoea and hoarseness (80%) were the symptoms that prompted presentation. Hashimoto’s thyroiditis was not found. The commonest histological subtype was diffuse large B cell lymphoma (45% of cases). Seven patients had stage I disease, 3 stage II and 1 stage IV. Nine patients received chemotherapy and radiotherapy was administered in the adjuvant setting to nearly half of the patients. No correlation between presentation and other diagnostic tests or survival was found. Two-year survival for our patients was 100% and no cases died from their disease. Conclusion: Thyroid lymphoma is a rare disease and valuable information on this subject has been provided by single institution studies. Our encouraging survival figures are likely a combination of the predominance of early stage disease and the use of combined modality therapy. The use of monoclonal antibodies may provide a further benefit to these patients. No significant financial relationships to disclose.

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Clinicopathological Characteristics and A20 (TNFAIP3) Mutation In Primary Thyroid Lymphoma

Blood ◽

10.1182/blood.v122.21.4320.4320 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4320-4320

Author(s):

Yasuko Hamada ◽

Mariko Ishibashi ◽

Toshio Asayama ◽

Namiko Okuyama ◽

Asaka Kondo ◽

...

Keyword(s):

B Cell ◽

Missense Mutation ◽

Malt Lymphoma ◽

Hashimoto’S Thyroiditis ◽

Genomic Dna ◽

B Cell Lymphoma ◽

Negative Regulator ◽

Hashimoto's Thyroiditis ◽

Thyroid Lymphoma ◽

Primary Thyroid Lymphoma

Abstract Background Primary thyroid lymphoma (PTL) is rare, composing approximately 5% of all thyroid malignancies, 1–2.5% of all malignant lymphomas, and fewer than 3% of all extranodal lymphomas. PTL frequently arises in a background of autoimmune thyroid disease, especially Hashimoto’s thyroiditis, but the genetic basis is largely unknown. The NF-κB negative regulator A20, also called tumor necrosis factor-α-induced protein 3 (TNFAIP3), has recently been reported to be frequently inactivated by deletion and/or mutation, which are involved in the pathogenesis of subsets of B-cell lymphomas, especially mucosa-associated lymphoid tissue (MALT) lymphoma. A20 deletion occurs more frequently in ocular adnexa and salivary MALT lymphoma, but there have been very few reports of it in PTL. In this study, we first analyzed the clinicopathologic characteristics of PTL and then investigated whether A20 inactivation by mutation or deletion was frequently detected in PTL. Patients and Methods We retrospectively analyzed 34 PTL patients treated from 2002 to 2013 in our institutions and diagnosed according to the 2008 WHO classification. A20 mutations were examined by directly sequencing genomic DNA using a set of primers. Results The patients included 9 men and 25 women, median age 68 (range, 35–84) years, presenting with a rapidly growing nodular goiter with or without cervical adenopathy (n=30), hoarseness (n=1), or without symptoms related to lymphoma or hypothyroidism (n=3). The pathologic diagnosis of PTL included diffuse large B-cell lymphoma (DLBCL) (n=20), DLBCL with MALT (n=1), and MALT lymphoma (n=13). Twenty-one (62%) had a previous history of Hashimoto’s thyroiditis, and 6 were diagnosed with that condition concurrently with lymphoma. The majority of patients (n=23, 67%) had stage IE disease, although 8 (27%) had stage IIE disease and 3 advanced stage. Compared with MALT lymphoma, the patients with DLBCL presented with larger tumor size including bulky mass (>10 cm), elevated lactate dehydrogenase level, and poor prognosis (relapse rate, 25%) despite receiving THP-COP or CHOP combination therapy with rituximab. MALT lymphoma patients with total thyroidectomy had a good prognosis without chemotherapy; the disease-free survival rate was 100% in the median 40.5-month follow-up. We did not find any routine clinical or biological factors that predicted the evolution from Hashimoto’s thyroiditis to MALT lymphoma. Next, we analyzed A20 mutations in genomic DNA extracted from 16 samples. A20 mutations were identified in 2 of 13 PTL patients examined (15%): 1 of 6 (17%) with DLBCL and 1 of 7 (14%) with MALT lymphoma. Both patients with A20 mutations had Hashimoto’s thyroiditis. Interestingly, the 2 had a common missense mutation in exon 3 (rs2230926 380T>G; F127C), which reduces the ability of A20 to inhibit NF-kB signaling. In one patient, this missense mutation was newly acquired after chemotherapy and radiation. Conclusion We confirmed the histologic heterogeneity of PTL corresponding to different clinical presentations and different prognoses. A20 abnormalities may be related to PTL pathogenesis in some patients. Disclosures: No relevant conflicts of interest to declare.

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Diffuse Large B-cell Lymphoma of thyroid gland in an Adolescent girl with Hashimoto’s thyroiditis

Endocrine Abstracts ◽

10.1530/endoabs.70.aep876 ◽

2020 ◽

Author(s):

Mara Xatzipsalti ◽

Evangelos Bourousis ◽

Maria Nikita ◽

Myrsini Gkeli ◽

Evgenia Magkou ◽

...

Keyword(s):

Thyroid Gland ◽

B Cell ◽

Hashimoto’S Thyroiditis ◽

Adolescent Girl ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Hashimoto's Thyroiditis ◽

Large B Cell Lymphoma ◽

Large B Cell

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Lymphocyte-predominant Hodgkin lymphoma: what is the optimal treatment?

Hematology ◽

10.1182/asheducation-2013.1.406 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 406-413 ◽

Cited By ~ 9

Author(s):

Michelle Fanale

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Radiation Treatment ◽

Early Stage ◽

B Cell Lymphoma ◽

B Cell Lymphomas ◽

Early Stage Disease ◽

Stage Disease ◽

Relapsed Disease

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a unique diagnostic entity, with only ∼ 500 new cases in the United States per year with a similar infrequent incidence worldwide. NLPHL also has distinctive pathobiology and clinical characteristics compared with the more common classical Hodgkin lymphoma (cHL), including CD20 positivity of the pathognomic lymphocytic and histiocytic cells and an overall more indolent course with a higher likelihood of delayed relapses. Given the limited numbers of prospective NLPHL-focused trials, management algorithms historically have typically been centered on retrospective data with guidelines often adopted from cHL and indolent B-cell lymphoma treatment approaches. Key recent publications have delineated that NLPHL has a higher level of pathological overlap with cHL and the aggressive B-cell lymphomas than with indolent B-cell lymphomas. Over the past decade, there has been a series of NLPHL publications that evaluated the role of rituximab in the frontline and relapsed setting, described the relative incidence of transformation to aggressive B-cell lymphomas, weighed the benefit of addition of chemotherapy to radiation treatment for patients with early-stage disease, considered what should be the preferred chemotherapy regimen for advanced-stage disease, and even assessed the potential role of autologous stem cell transplantation for the management of relapsed disease. General themes within the consensus guidelines include the role for radiation treatment as a monotherapy for early-stage disease, the value of large B-cell lymphoma–directed regimens for transformed disease, the utility of rituximab for treatment of relapsed disease, and, in the pediatric setting, the role of surgical management alone for patients with early-stage disease.

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Cell Of Origin Does Not Affect Outcomes In Early Stage Non-Bulky Diffuse Large B-Cell Lymphoma Treated With Short-Course Combined Modality Therapy

Blood ◽

10.1182/blood.v122.21.3017.3017 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3017-3017 ◽

Cited By ~ 1

Author(s):

Matthew A. Lunning ◽

Jocelyn C. Maragulia ◽

Anita Kumar ◽

Martin Bast ◽

Philip Bierman ◽

...

Keyword(s):

B Cell ◽

Early Stage ◽

Combined Modality Therapy ◽

B Cell Lymphoma ◽

Cell Of Origin ◽

Bulky Disease ◽

Large B Cell Lymphoma ◽

Short Course ◽

Ann Arbor ◽

Disease Free

Abstract Introduction Early stage non-bulky disease accounts for approximately 25% of all cases of diffuse large B-cell lymphoma (DLBCL). An effective treatment regimen for early stage non-bulky DLBCL is short-course combined modality therapy (CMT) as evidenced by the SWOG 0014 study that reported 4-year PFS and OS of 88% and 92%, respectively (Persky D et al. JCO 2008). The cell of origin (COO) of DLBCL can be classified based on immunohistochemistry (Hans criteria) and gene expression profiling (GEP) into two clinically recognized cohorts: germinal center B-cell-like (GCB) and non-GCB phenotypes. The Hans immunohistochemistry-based algorithm reproduced the GEP classification in 71% of GCB and 88% of non-GCB cases (Hans CP Blood 2004). In patients with advanced stage DLBCL, patients with a non-GCB phenotype had a significantly worse 5-year overall survival. There is a paucity of data regarding the prognostic significance of COO in early stage non-bulky DLBCL. In one report of early stage DLBCL by GEP, GCB phenotype accounts for approximately 77% of cases (Rosenwald et al. NEJM 2002). The outcomes of early stage non-bulky DLBCL patients treated with CMT segregated by COO is unknown. Methods To investigate the outcomes of early stage non-bulky DLBCL and impact of COO, we conducted a retrospective review of all patients with DLBCL or follicular lymphoma grade 3b treated with short-course rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy plus involved-field radiation therapy (IFRT) between 2000 and 2012 at Memorial Sloan-Kettering Cancer Center (MSKCC) and the University of Nebraska Medical Center (UNMC). Individual chart review was performed to extract the clinical presentation, pathological features, treatments, and outcomes. Early stage non-bulky DLBCL was defined as Ann Arbor stage I or stage II, non-bulky (without a mass ≥ 10 cm). The stage-modified international prognostic index (SM-IPI) defined as stage lI (vs.I), age>60, elevated LDH, and ECOG performance status ≥ 2 was calculated if all variables were available. The Hans algorithm and/or GEP were used to classify patients as either GCB or non-GCB. Short-course CMT was defined as R-CHOP for 3 or 4 cycles plus IFRT. Disease free survival and overall survival were calculated using Kaplan Meier analysis. Results In total 97 patients were evaluated with a median age of 58 (range 19 to 83) with 52% woman. The majority (90%) of patients had DLBCL (versus follicular lymphoma grade 3b) and 79% had Ann Arbor stage I/IE disease. There were no patients with bulky disease in this series. The SM-IPI characteristics are listed in Table 1a. COO was determined by the Hans algorithm in 94 of 97 cases (97%), by Hans and GEP in 2 cases, and by GEP alone in one case. A GCB phenotype was seen in 76% of the patients. In the 74 (76%) patients with all SM-IPI variables extracted, 31% patients had 0 risk factors, 50% had 1 risk factor, and 19% had 2 or 3 risk factors. The SM-IPI was not significant (p> 0.05; NS) between the GCB and non-GCB cohorts (See Table 1b). The majority (68%) received R-CHOP for 3 cycles with the remaining receiving 4 cycles. One patient had a contraindication to vincristine thus etoposide was substituted (R-CHEP). Subsequent IFRT was given to all patients. At a median follow-up among survivors of 52 months, 97% of patients remained alive and 94% remained disease free. At 52 months, all patients in the non-GCB cohort remained disease free and in the GCB cohort 92% were disease free (p=0.821). Overall, 6 deaths have occurred: 2 related to disease, 2 of unknown cause, and 2 unrelated to disease. Conclusions Patients with early stage non-bulky DLBCL treated with short-course CMT continue to have an excellent prognosis. Our data confirms prior GEP data that the GCB phenotype, by immunohistochemistry-based Hans algorithm, is predominantly seen in early stage non-bulky DLBCL. In contrast to advanced stage DLBCL, COO does not appear to influence outcomes in early stage non-bulky DLBCL with this treatment approach. Disclosures: Horwitz: Celgene, Allos, Seattle Genetics, Bristol-Myers Squibb, Genzyme, Kyowa, Janssen, Johnson & Johnson, Millenium: Consultancy; Celgene, Allos, Seattle Genetics, Kyowa, Infinty, Millenium: Research Funding.

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Primary Mediastinal B-Cell Lymphoma: The Dilemma of Radiotherapy

Blood ◽

10.1182/blood-2020-140021 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 30-31

Author(s):

Filipa Saraiva ◽

Christopher J. Saunders ◽

Margarida Fevereiro ◽

Alexandra Monteiro ◽

Aida B Sousa

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Early Stage ◽

Autologous Transplantation ◽

B Cell Lymphoma ◽

Molecular Characteristics ◽

Early Stage Disease ◽

Free Survival ◽

Stage Disease

Introduction: According to the WHO classification, primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a distinct entity, which has a close relationship with nodular sclerosing classical Hodgkin's lymphoma (cHL) in terms of clinical and molecular characteristics and sharing an excellent prognosis. When PMBCL is treated with R-CHOP, the addition of radiotherapy (RT) turns more than 90% of positron emission tomography (PET) positive cases into complete remissions (CR) and increases 5-year overall survival (OS) to 93%. However, the fear of potential late toxicities due to RT, has led an increasing number of centers to favor more intensive regimens like DA-EPOCH-R without RT. This controversy is deepened by the recent comparison between the latter regime with R-CHOP, unfavorable to the DA-EPOCH-R for toxicity reasons. Objective: Evaluate the effectiveness and late toxicities of R-CHOP plus RT in our center and secondarily compare these results with the ones obtained in our cHL patients with bulky and early stage disease. Methods: Retrospective analysis of patients with PMBCL treated between Jan/2007 and Dec/2017 according to clinical characteristics, late toxicities, rate of CR, OS and disease-free survival (DFS) estimated by Kaplan-Meier method. Results: In 32 patients with a median age of 34 years (23-70), 56% were male, 91% had limited stage and 6% had an unfavorable IPI. The rate of CR was 91% (2 patients needed second line therapy to achieve CR) with 2 relapses (at 6 and 11 months, respectively) rescued with autologous transplantation. Three deaths were recorded due to disease progression. With a median follow-up of 86 months, OS and DFS at 10 years were 91% and 93%, respectively. As for late toxicities, besides 2 cases of severe pulmonary fibrosis, there were no other relevant late toxicities registered. These results overlap those obtained in our cHL patients with bulky and early stage disease treated with Stanford V plus RT with an OS and an event free survival of 93% and 84%, respectively. Conclusion: These results support PMBCL's excellent prognosis, parallel to that of cHL. Given the low probability of late toxicities with this regimen our data uphold against the therapeutic strategy of more intensive regimens, that have an increased management complexity and are clinically more toxic. Disclosures No relevant conflicts of interest to declare.

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Primary thyroid high‐grade B‐cell lymphoma with MYC and BCL2 rearrangements in Hashimoto's thyroiditis

Diagnostic Cytopathology ◽

10.1002/dc.24922 ◽

2021 ◽

Author(s):

Hamza Tariq ◽

Urooj Zahra

Keyword(s):

B Cell ◽

Hashimoto’S Thyroiditis ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Hashimoto's Thyroiditis ◽

High Grade

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Defining and Treating High-grade B-cell lymphoma, NOS

Blood ◽

10.1182/blood.2020008374 ◽

2021 ◽

Author(s):

Adam Olszewski ◽

Habibe Kurt ◽

Andrew M Evens

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Early Stage ◽

Diagnostic Category ◽

B Cell Lymphoma ◽

Cell Phenotype ◽

High Grade ◽

Early Stage Disease ◽

Pathologic Classification ◽

Disseminated Disease

High-grade B-cell lymphoma, not otherwise specified (HGBL, NOS) is a recently introduced diagnostic category for aggressive B-cell lymphomas. It includes tumors with Burkitt-like or blastoid morphology that do not have double-hit cytogenetics and that cannot be classified as other well-defined lymphoma subtypes. HBCL, NOS are rare and heterogeneous; most have germinal center B-cell phenotype, and up to 45% carry a single-hit MYC rearrangement, but otherwise they have no unifying immunophenotypic or cytogenetic characteristics. Recent analyses utilizing gene expression profiling (GEP) revealed that up to 15% of tumors currently classified as diffuse large B-cell lymphoma display a HGBL-like GEP signature, indicating a potential to significantly expand the HGBL category using more objective molecular criteria. Optimal treatment of HGBL, NOS is poorly defined due to its rarity and inconsistent diagnostic patterns. A minority of patients have early-stage disease which can be managed with standard RCHOP-based approaches with or without radiation. For advanced-stage HGBL, NOS, which often presents with aggressive, disseminated disease, high lactate dehydrogenase, and involvement of extranodal organs (including the central nervous system [CNS]), intensified Burkitt lymphoma-like regimens with CNS prophylaxis may be appropriate. However, many patients diagnosed at age > 60 years are not eligible for intensive immunochemotherapy. An improved, GEP and/or genomic-based pathologic classification that could facilitate HGBL-specific trials is needed to improve outcomes for all patients. In this review, we discuss the current clinicopathologic concept of HGBL, NOS, existing data on its prognosis and treatment, and delineate potential future taxonomy enrichments based on emerging molecular diagnostics.

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