Mantle Cell Lymphoma: Combined Extranodal/Nodal Involvement of The Head And Neck With Multifocal Oral Manifestation

Abstract Background: Mantle Cell Lymphoma (MCL) is a rare sub-type of Non-Hodgkin's Lymphoma (NHL). Outcomes of secondary MCL (sMCL) in patients with a prior diagnosis of a solid malignancy as compared to de novo MCL are not well understood. Differences may be attributable to age, gender, race/ethnicity, extra-nodal involvement, and stage at initial diagnosis. We sought to determine differences in outcome by analyzing data from a large nationwide cancer registry. Methods: The Surveillance Epidemiology and End Results (SEER) database (1973-2012) was used to detect MCL (ICD-O-3 code: 9673/3) adult (>18 years) cases. The variable "First Malignant Primary Indicator" was used to differentiate between de novo and sMCL cases. Primary solid malignancy subtypes categorized included prostate, breast, colorectal, lung bladder, renal, head and neck, thyroid, testicular, and endometrial cancer. Selected sMCL cases included patients with a diagnosis of a primary solid malignancy with a latency period ≥ 2 months. Overall survival (OS) was calculated using the cox regression model to determine the impact of sMCL on survival, adjusting for age at diagnosis, race/ethnicity, primary solid malignancy subtype type and latency period. Chi square test was utilized to ascertain for any significant difference between de novo MCL and sMCL cases. Results: Overall, 8,889 patients were included: 875 (9.8%) sMCL and 8,014 (90.2%) de novo MCL cases. For de novo MCL, 67.1% were males. Race/ethnicity in descending frequency consisted of Non-Hispanic Whites (NHW) (81.8%), Hispanics (8.4%), Blacks (4.4%), Asian and Pacific Islanders(API)(4.1%) and American Indian/Native Indian (AI) (0.4%). The most frequent stage at initial diagnosis for de novo MCL was stage IV (57.9%) followed by stage III (13.4%), stage II (8.1%) and stage I (10.0%). Males consisted of 75.4% of sMCL cases. Cases of sMCL categorized by race/ethnicity in descending frequency were NHW (87.3%), Hispanics (5.1%), Blacks (4.2%), API (3.2%) and AI (0.1%). Stage at diagnosis for sMCL was most frequently stage IV (54.6%), followed by stage III (15.8%), stage II (10.9%) and stage I (11.7%). Compared to de novo MCL, sMCL cases were more likely to occur in patient's ≥75 years (48.3% vs. 28.7%, p<0.01). An absence of extra-nodal involvement at diagnosis was common in both de novo MCL (84.0%) and sMCL (83.7%). Specific to sMCL cases, more than 90% of primary solid malignancies were limited to local/regional involvement. All primary solid malignancy subtypes except for head and neck (48 months) and renal cancer (59 months) had a latency period of greater 5 years. Median OS was significantly worse in sMCL (34 months) compared to de novo MCL (53 months) (HR: 1.375, 95% CI:1.243-1.504). Conclusion: Our analysis demonstrates that elderly age appears to be significantly more common in sMCL cases as compared to de novo MCL. By contrast, race/ethnicity, and extra-nodal involvement were similar between the two groups. Survival was worse in sMCL compared to de novo MCL. This may be due to differences in treatment preferences. Further studies are necessary to elucidate the etiology for such differences in outcomes. Disclosures Kropf: Teva Pharmaceuticals: Consultancy.

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Indolent mantle cell lymphoma with nodal involvement and mutated immunoglobulin heavy chain genes

Human Pathology ◽

10.1053/s0046-8177(03)00410-6 ◽

2003 ◽

Vol 34 (10) ◽

pp. 1030-1034 ◽

Cited By ~ 76

Author(s):

Laurentia Nodit ◽

David W Bahler ◽

Samuel A Jacobs ◽

Joseph Locker ◽

Steven H Swerdlow

Keyword(s):

Mantle Cell Lymphoma ◽

Heavy Chain ◽

Cell Lymphoma ◽

Immunoglobulin Heavy Chain ◽

Nodal Involvement ◽

Mantle Cell ◽

Immunoglobulin Heavy Chain Genes

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Extranodal Head and Neck Mantle Cell Lymphoma: Characteristics, Treatment, and Survival

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894211025171 ◽

2021 ◽

pp. 000348942110251

Author(s):

Christopher T. Breen ◽

Janet Chao ◽

Saral Mehra ◽

Nikita Kohli

Keyword(s):

Mantle Cell Lymphoma ◽

Head And Neck ◽

Cumulative Incidence ◽

Cell Lymphoma ◽

Early Stage ◽

Anatomic Site ◽

Early Stage Disease ◽

Stage Disease ◽

Significant Difference ◽

Mantle Cell

Objectives: To describe disease characteristics and treatment and to analyze survival and mortality for extranodal mantle cell lymphoma (MCL) of the head and neck. Methods: Patients with extranodal MCL—excluding primary sites in the salivary glands, eye, and adnexa—were identified from the Surveillance, Epidemiology, and End Results (SEER) 18 Registries (2000-2015). Overall survival (OS) and cumulative incidence of MCL and non-MCL mortality were calculated. Factors associated with MCL and non-MCL mortality were analyzed with cause-specific hazard models. Results: Five hundred nine patients met criteria for descriptive analysis and 294 patients met criteria for survival analysis, with a median follow-up of 58 months. The most common sites for MCL were the oropharynx (66.0%), nasopharynx (19.1%), and oral cavity (8.4%). The most common treatment received was chemotherapy alone (48.9%), followed by chemoradiation therapy (16.9%), and radiation therapy alone (10.4%). The proportion of cases diagnosed as early-stage disease ranged from 31% of sinonasal MCLs to 83% of laryngeal MCLs. At 5 years, OS was 63% (95% CI: 57%-69%). There was no significant difference in OS ( P = .79), cumulative incidence of MCL mortality ( P = .76), or cumulative incidence of non-MCL mortality ( P = .98) by anatomic site. Comparing early-stage to late-stage disease, there was no significant difference in OS ( P = .38), cumulative incidence of MCL mortality ( P = .07), or cumulative incidence of non-MCL mortality ( P = .14). Multivariate analysis showed increased hazard of MCL mortality for patients that were older or that presented with stage III or stage IV disease. Conclusion: The oropharynx is the most common subsite of head and neck MCLs, followed by the nasopharynx. Primary head and neck MCLs appear to present at an earlier stage than MCLs of other regions. In particular, laryngeal and hypopharyngeal MCLs may present as stage I or II disease.

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Gene Expression Profiling Using Nanostring™ Reveals Differences According to Location, Histology and MIPI Score in Mantle Cell Lymphoma

Blood ◽

10.1182/blood-2019-132056 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5218-5218

Author(s):

Diana Lucia Martínez Baquero ◽

Ken H. Young ◽

Roberto N. Miranda ◽

L. Jeffrey Medeiros ◽

Chi Young Ok

Keyword(s):

Gene Expression ◽

Mantle Cell Lymphoma ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Cell Lymphoma ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Nodal Involvement ◽

Lymphoma Cells ◽

Mantle Cell

Background Mantle cell lymphoma (MCL) is an aggressive B cell neoplasm characterized the by t(11;14)(q13;q32)/CCND1-IGH resulting in overexpression of cyclin D1. Although indolent variants are recognized, MCL is generally aggressive and incurable. The MCL International Prognostic Index (MIPI), gene expression-based proliferation signatures, Ki-67 proliferation index, p53 expression, and aggressive histologic features are used for risk stratification, but the prognostic groups defined by each of these markers are clinically heterogeneous, demonstrating that each parameter alone does not fully account for the clinical behavior of these tumors. In this study, we investigated the gene expression profile of 60 cases of MCL and evaluated which genes had expression patterns that correlate with different clinical and histopathological parameters. Design A total of 60 excisional biopsy specimens of MCL were selected for gene expression profiling. Forty (66%) and 16 (26%) cases were untreated and relapse/persistent samples, respectively; in 4 this unknown was unknown. Biopsy sites included lymph nodes (n=38), spleen (n=10), tonsil (n=6) and various other extranodal tissue sites (n=6). The morphologic features were classic in 27 and aggressive (blastoid/pleomorphic) in 33 patients. MIPI was calculated in selected patients with nodal involvement and whose biopsy was an obtained prior to treatment. Each block contained tumor cells representing ≥ 80% of all cells in the biopsy specimen. RNA was extracted from formalin-fixed paraffin-embedded tissue using the Qiagen Allprep FFPE Kit after deparaffinization, according to the manufacturer's instructions. Gene expression was quantified in 200ng of RNA on the Nanostring™ platform. Normalization for RNA loading was performed using the geometric mean of 40 housekeeping genes with a cutoff value 20. Standard QC and data processing were performed using the nSolver™ Analysis Software. Adjusted p-values were used according to the Benjamini-Hochberg procedure. Results Gene expression profiling was different according to the site of involvement of MCL. Compared with nodal involvement, MCL involving spleen showed overexpression of VEGFA (p <0.01) and NOS (p <0.05). These genes are associated with angiogenesis via the PI3K signaling pathway. Similarly, tonsillar MCL showed overexpression of SFN and HSPB1 (p <0.01) compared with nodal MCL; these genes are related to the MAPK pathway. Different gene expression profiles were observed with respect to histology. Compared to classic variant, blastoid variant demonstrated overexpression of CDK4 (p <0.01) and underexpression of KAT2B and PIK3CG (p <0.01) in all cases. However, no significant differences were found in the gene expression profiles between the classic and pleomorphic variants. We also compared gene expression profiles based on the MIPI score. Compared to cases with a low MIPI score, those with a high MIPI score showed significant overexpression of several genes including SFN, COL11A2, HDAC6 and TP53 (p <0.01). Discussion MCL is a heterogeneous neoplasm, both clinically and genetically. In the present study, significant differences in gene expression profiles were observed based on site of involvement (spleen vs lymph node vs tonsil). However, we cannot exclude the possibility that the result reflects gene expression of non-lymphoma cells in the microenvironment since we did not extract RNA from lymphoma cells. We observed different gene expression profiles in the blastoid variant, but not in the pleomorphic variant compared to the classic variant, suggesting that the biology of pleomorphic variant is probably between the blastoid and the classic variants, possibly closer to the latter. Different gene expression profiles were found with respect to MIPI score, providing scientific support that the MIPI score, in addition to being a useful stratification factor in MCL patients, is reflecting differences in underlying biology of MCL. Disclosures No relevant conflicts of interest to declare.

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