Extranodal lymphomas of the head and neck

Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck and may involve nodal or extranodal sites. Nodal head and neck lymphomas are similar to other nodal sites and are not further reviewed here. The head and neck region is the second most frequent anatomical site of extranodal lymphomas (after the gastrointestinal tract). Most are non-Hodgkin's lymphomas of B-cell lineage, and overall diffuse large B-cell lymphoma is the most common type. Hodgkin's lymphoma rarely occurs in extranodal sites. Other hematologic neoplasms that commonly involve extranodal sites of the head and neck are also discussed. In this review, we begin by discussing lymphomas involving the head and neck according to anatomical site. Then we discuss specifically the pathological findings of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, plasmablastic lymphoma, extramedullary plasmacytoma, and extranodal natural killer/T-cell lymphoma of nasal type.     

Extranodal mantle cell lymphoma mimicking marginal zone cell lymphoma

AIM: We report a case of mantle cell lymphoma masquerading as a marginal zone cell lymphoma. METHODS AND RESULTS: In the initial manifestation in the palatine tonsils, the neoplastic cells were found to grow exclusively within the marginal zones of secondary follicles which showed a preserved mantle zone. The few immunostains performed showed a B-cell phenotype including an immunoglobulin light chain restriction. The extranodal manifestation, the growth pattern, and the immunophenotype led to the diagnosis of an extranodal marginal zone B-cell non-Hodgkin's lymphoma (NHL). The specimen from the relapse occurring 8 months later exhibited diffuse monomorphous cells co-expressing B-cell antigens and CD5, CD43 and cyclin D1, leading to the diagnosis of mantle cell lymphoma. Re-investigation of the initial biopsy revealed that the neoplastic cells within the marginal zones had a mantle cell lymphoma immunophenotype expressing cyclin D1, the immunoglobulin heavy chains IgD and IgM and partly CD5. Both lesions harboured identical clonal immunoglobulin gene rearrangements proving that they represented different manifestations of the same lymphoma. CONCLUSION: This case emphasizes the importance of broad immunohistological investigation of B-cell NHLs involving the marginal zone.     

Composite marginal zone B-cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 cases

AIMS: Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B-cell non-Hodgkin's lymphoma (B-NHL). We characterized 12 cases of composite marginal zone B-cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology. METHODS AND RESULTS: Eight patients had gastric MZBL of mucosa-associated lymphoid tissue (MALT)-type, in five cases with a diffuse large B-cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT-type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin- and Reed-Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein-Barr virus-associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT-type and cHL. CONCLUSIONS: MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT-type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.     

Analysis of 1983 cases of malignant lymphoma in Thailand according to the World Health Organization classification

Studying a large series of malignant lymphoma is important to increasing our understanding of this disease. Based on the World Health Organization classification system, 1983 cases of lymphoma at Siriraj Hospital were classified as either non-Hodgkin lymphoma (NHL) (92.1%) or Hodgkin lymphoma (HL) (7.9%). The NHL cases were 75% B cell type and 25% T cell type. Diffuse large B-cell lymphoma, unspecified peripheral T-cell lymphoma, follicular lymphoma, extranodal marginal zone B-cell lymphoma, precursor T lymphoblastic lymphoma, and Burkitt lymphoma accounted for 84.3% of all NHL cases found. Mixed cellularity and nodular sclerosis types constituted 77.7% of the HL cases found. An overall male preponderance was observed, but sex distribution differed among various types of lymphoma, and a female preponderance was observed in the elderly subjects. Changes in the frequency of B-cell NHL by age were characteristic: <50% in the first decade of life, a further decrease in the second decade, >60% in the third decade, and increases thereafter, reaching 90% after the seventh decade. High frequency of follicular lymphoma in Bangkok but low frequency in the Northeastern region and high frequency of HL in the Southern region were significant (P <0.05). Extranodal involvement was observed in 58.7% of NHLs, commonly affecting the upper aerodigestive tract and gastrointestinal tract, with some differences in geographical distribution. Higher frequencies of T-cell NHLs involving extranodal sites and of B-cell NHLs involving lymph nodes were significant (P <0.05). The distribution of various types of lymphoma and comparison with other large series of lymphoma further demonstrates the heterogeneity of this disease.     

Lymphomas and lymphoproliferative diseases of the lung

Primary pulmonary lymphoma is a rare disease and the majority of cases represent extranodal marginal zone lymphoma, followed by diffuse large B-cell lymphoma. Other lymphomas that commonly involve the lung include lymphomatoid granulomatosis, a neoplasm of large EBV-positive B cells that are typically outnumbered by non-neoplastic T cells, and classical Hodgkin's lymphoma, which usually reflects systemic dissemination or direct mediastinal extension. The differential diagnosis of marginal zone lymphoma includes secondary involvement by other systemic low-grade B-cell lymphomas and chronic reactive conditions, such as nodular lymphoid hyperplasia, while the other entities elicit a differential diagnosis that includes various high-grade lymphoid neoplasms. A specific diagnosis can usually be achieved on the basis of histological evaluation and immunophenotyping, although molecular genetic studies may be required in certain situations. Such a multiparameter approach may be warranted to accurately diagnose these entities due to differing clinical implications in terms of prognosis and treatment.     

Lymphoid neoplasms of the sinonasal tract and their differential diagnoses

Many types of lymphoid neoplasms have been reported involving the sinonasal region including aggressive and indolent B-cell lymphomas, T/NK cell lymphomas and plasma cell neoplasms. They account for a small percentage of all lymphomas but as a whole is the second most common malignancy in the sinonasal region. Clinically and morphologically, they can mimic non-neoplastic and non-hematolymphoid malignant lesions in this region and must be included in the differential diagnoses when a sinonasal lesion is encountered. This article describes the histopathologic and molecular features of diffuse large B-cell lymphoma and extranodal NK/T cell lymphoma, the two main types of lymphomas found in the sinonasal tract, as well as plasmacytoma and plasmablastic lymphoma, which tend to locate in the head and neck region, and reviews the main differential diagnoses.     

Fine-needle aspiration cytology of extranodal lymphoma

The assessment of lymphoproliferative disorders using fine-needle aspriation (FNA) cytology may be problematic particularly when organs other than lymph node are involved. In this report we have reviewed 26 consecutive FNA specimens from superficial extranodal sites which were reported as diagnostic or suggestive of malignant lymphoma. The aspirates were obtained from skin or subcutaneous tissue (ten cases), thyroid (five cases), salivary gland (five cases), breast (four cases), neck, and pharynx (one case each). Ancillary studies including immunocytochemistry, in situ hybridisation to detect immunoglobulin light chain mRNA expression, and polymerase chain reaction for analysis of immunoglobulin heavy chain gene rearrangement were performed in 20, 12, and 7 cases, respectively. Clinicopathologic correlation confirmed the diagnosis of lymphoma in 25/26 aspirates. Nine of the 14 patients whose initial presentation was with an extranodal mass were considered to have primary lymphomas of mucosa-associated lymphoid tissue (MALT) type. In contrast, ten of 11 patients with recurrent extranodal disease had primary nodal type lymphomas. There was one false-positive diagnosis, a neck mass misinterpreted cytologically as B-cell lymphoma which was ultimately shown to be a branchial cyst. FNA cytology supported by appropriate ancillary investigations provides accurate diagnosis in most cases of extranodal lymphoma. Diagn. Cytopathol. 1998;19:260–266. © 1998 Wiley-Liss, Inc.     

CD5-undetected by immunohistochemistry, t(11;14)(q13;q32)-positive conjunctival mantle cell lymphoma: a case report

Most primary ocular adnexal lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). A few cases of ocular adnexal mantle cell lymphomas have been reported in the literature. We present a case of mantle cell lymphoma presenting as conjunctival mass. A 58-year-old man presented with a palpable mass in the left lower tarsal conjunctiva incidentally detected one month previously. Histopathologic examination showed proliferation of monomorphous small-to-medium sized lymphoid cells. On immunohistochemistry, tumor cells were positive for CD20, bcl-2, and cyclin D1, and negative for CD5. PCR analysis for immunoglobulin heavy chain gene rearrangement showed monoclonal B-cell proliferation. t(11;14)(q13;q32), involving the CCND1 and IGH genes, was detected in interphase fluorescent in situ hybridization using formalin-fixed, paraffin-embedded tissue; however, MALT1 gene translocation was not observed. The final diagnosis was mantle cell lymphoma. There was no lymphadenopathy; however, bone marrow involvement of the lymphoma was suspected. The patient has been receiving systemic chemotherapy. This case emphasizes the differential diagnosis of conjunctival mantle cell lymphoma from extranodal marginal zone B-cell lymphomas of MALT regarding the clinical and pathological aspects.     

ALK-positive diffuse large B-cell lymphoma of the stomach associated with a clathrin-ALK rearrangement

ALK-positive diffuse large B-cell lymphoma is a rare, recently characterized lymphoma subtype that shows granular cytoplasmic ALK expression. This report describes a primary gastric ALK-positive B-lineage lymphoma in which a clathrin (CLTC)-ALK fusion was identified by RT-PCR and direct sequencing of the breakpoint. This confirmed the presence of t(2;17)(p23;q23) involving the CLTC gene and is only the 4th report of such a translocation in this lymphoma subtype and the first to describe this tumor within the stomach. As in previous reports, immunophenotyping showed the malignant cell to be a terminally differentiated B-lineage cell characterized by the absence of B-cell antigens and expression of antigens associated with plasma cell differentiation. This case confirms the existence of such a lymphoma subtype arising in extranodal locations and underscores the importance of detailed immunophenotyping and specialized molecular genetic investigations in confirming the diagnosis.     

Expression of Smac/DIABLO in B-cell non-Hodgkin and Hodgkin lymphomas

Inhibitor of apoptosis proteins (IAPs) are upregulated in cancers and suppress cell death, in part, through their ability to directly inhibit caspases. Inhibitor of apoptosis proteins are differentially expressed in B-cell lymphomas. The functions of some IAPs are counteracted by the cell death inducer, second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO). In this study, we investigated the expression levels of Smac/DIABLO in 14 lymphoma cell lines by Western blot analysis. We also assessed 247 B-cell non-Hodgkin's lymphoma (NHL) and 40 Hodgkin's lymphoma (HL) tumors using immunohistochemical methods. Smac/DIABLO was expressed in most NHL and all HL cell lines. In NHL, Smac/DIABLO was expressed in 117 (47%) tumors and was differentially expressed in various NHL types. In most NHLs, from 29% to 68% of tumors were positive; however, Smac/DIABLO was not detected in small lymphocytic lymphoma/chronic lymphocytic leukemia and Burkitt lymphoma, and was rare in extranodal marginal zone B-cell lymphoma. In HL, Smac/DIABLO was positive in 25 (63%) tumors. Unlike NHL, all types of HL were positive for Smac/DIABLO, although nodular sclerosis was least often positive. The differential expression of Smac/DIABLO in NHLs suggests that apoptotic mechanisms are differentially involved in their pathogenesis. These results may also have implications for using Smac/DIABLO or its agonists as therapeutic agents.     

From lymphocytic interstitial pneumonia to MALT lymphoma of lung: a case report with a 5-year diagnostic dilemma

Lymphocytic interstitial pneumonia (LIP) and mucosa-associated lymphoid tissue (MALT) lymphoma of lung are all uncommon disorders of respiratory system. MALT lymphoma of lung is a distinct and unique subtype of marginal zone B-cell non-Hodgkin’s lymphoma (NHL) characterized by malignant cells arising from extranodal sites. They are characteristic of exuberant lymphoid infiltration in pathological tissue. Therefore, in some cases, they are too similar in clinical manifestation, chest imaging and pathology to make differential diagnosis. Here, we report a 43-year-old woman who underwent a tough process for the final diagnosis. From this case, we could get a well understanding of difference between LIP and MALT lymphoma of lung.     

Composite diffuse large B-cell lymphoma and CD20-positive peripheral T-cell lymphoma

Composite lymphoma is defined as two or more distinct types of lymphoma in a single anatomical site. Among various combinations, composite B-cell and T-cell non-Hodgkin's lymphomas (CBTL) are very infrequent. Herein we describe a 66-year-old female with CBTL presenting with lymphadenopathy, multiple bone lesions and an epidural tumor. Light microscopic examination of a biopsied cervical node revealed a dual population of lymphoid cells: sheets of large cells admixed with medium-sized cells. The large cells expressed B-cell markers and showed immunoglobulin light chain restriction, consistent with diffuse large B-cell lymphoma (DLBCL). The medium-sized cells were positive for CD20 as well as T-cell markers. Because polymerase chain reaction amplification showed monoclonal rearrangement of the T-cell receptor β chain gene, this population was compatible with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). We therefore made a diagnosis of composite DLBCL and CD20-positive PTCL-NOS. Complete remission was achieved after six cycles of R-CHOP regimen (rituximab, doxorubicin, vincristine, cyclophosphamide and prednisolone). This is the first report of CD20-positive PTCL-NOS associated with composite lymphoma. Moreover, a literature review of composite DLBCL and PTCL-NOS indicates that this rare clinical entity may be featured by efficacy of systemic chemotherapy in spite of prevalent extranodal lesions.     

Translocation (5; 11) in a conjunctival MALT lymphoma

Lymphoma is the most frequent malignant tumor of the ocular adnexa with the most common histologic type being extranodal marginal zone B-cell lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT lymphoma). Here we report a case of a 28 year-old male who presented with a left conjunctival mass of one year duration. A diagnosis of primary MALT lymphoma of the conjunctiva was made based on morphologic and immunopheno-typic studies. Chromosome analysis revealed a male karyotype with a translocation t (5;11) (q33;p11.2) as the primary chromosomal abnormality, which, to the best of our knowledge, is the first reported translocation in MALT lym-phomas and ocular MALT lymphomas as well.     

Discordant lymphoma: MALT lymphoma of the stomach and follicular lymphoma of the parotid gland

More than one histological type of malignant lymphoma can occur simultaneously in an individual. The entity is classified as either composite or discordant lymphoma. Both types of lymphoma, particularly discordant lymphoma comprised of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma (MALT-L) and follicular lymphoma (FL), are rare. We report a case of discordant lymphoma comprising MALT-L in the stomach and FL in the parotid gland. The patient was a 50-year-old Japanese woman who visited the University Hospital of Showa (Tokyo, Japan) because a barium study showed erosive gastric lesions. A gastro-intestinal endoscopy was performed 2 months after the barium study, which showed irregular erosions throughout the stomach body. A gastric biopsy showed MALT-L, and Helicobacter pylori (H. pylori) infection was confirmed. The patient had noticed a painless and elastic hard tumor mass of about 2 cm in diameter in the area of the left parotid gland 6 months before the barium study. We removed the parotid gland tumor and diagnosed it as FL 6 months after the barium study. We were able to diagnose the MALT-L and FL by morphological, immunohistochemical and molecular analyses of paraffin-embedded sections. This appears to be the first reported case of MALT-L and FL occurring together as a discordant lymphoma.     

Lymphoplasmacytic lymphoma and other non-marginal zone lymphomas with plasmacytic differentiation

Small B-cell lymphomas with plasmacytic differentiation frequently present diagnostic challenges. Session 3 of the 2009 Society for Hematopathology/European Association for Haematopathology Workshop focused on lymphoplasmacytic lymphoma (LPL). The submitted cases illustrated classic examples of bone marrow-based and nodal LPL and cases with atypical features, including unusual phenotypes or involvement of extranodal sites. Several cases showed varying degrees of overlap with marginal zone lymphoma, and, as acknowledged in the 2008 World Health Organization classification, a definitive distinction between these 2 possibilities cannot always be established. Session 6 of the workshop focused on other non-marginal zone lymphomas that may display plasmacytic differentiation. This session highlights the wide variety of neoplasms that enter into the differential diagnosis of small B-cell lymphomas with plasmacytic differentiation and demonstrates the use of clinical features and ancillary studies in establishing an appropriate diagnosis by 2008 World Health Organization criteria.     

Combining fine-needle aspiration and flow cytometric immunophenotyping in evaluation of nodal and extranodal sites for possible lymphoma: A retrospective review

The relatively recent evaluation of nodal and extranodal sites for malignant lymphoma by combining fine-needle aspiration (FNA) and flow cytometric immunophenotyping (FCI) techniques has resulted in a most rapid, accurate method. Our study represents a comprehensive retrospective review of in vivo applications of these techniques to cases suspicious for malignant lymphoma. We report our findings, which support the usefulness of these techniques, particularly in diagnosis and staging of primary and recurrent B-cell lymphomas (BCL). The findings of necrosis and numerous polymorphonuclear cells in cases with a previous history of BCL demand tissue biopsy. Initial diagnosis of BCL by FNA and FCI may obviate tissue biopsy. Diagn. Cytopathol. 16:200–206, 1997. © 1997 Wiley-Liss, Inc.     

T-cell-rich B-cell lymphoma (TCRBCL): limitations in fine-needle aspiration cytodiagnosis

Exclusive reports on fine needle aspiration (FNA) cytodiagnosis of T-cell-rich B-cell lymphoma (TCRBCL) are scarce in literature. This report reflects the diagnostic difficulties associated with cytodiagnosis of this rare variant of diffuse large B-cell lymphoma. The study is based on 11 cases with age ranging from 16 to 63 years and a median of 50 years. Male to female ratio was 6:5. Ten cases presented with lymphadenopathy and one had lymphadenopathy as well as extranodal solid tumor. The initial cytodiagnosis was suggestive of TCRBCL in one case, TCRBCL/Hodgkin's lymphoma (HL) in three cases, TCRBCL/HL/anaplastic large cell lymphoma (ALCL) in two cases, TCRBCL/ALCL in one case, and TCRBCL/non-Hodgkin lymphoma (NHL) T-cell/ALCL in one case. There was also a cytologically diagnosed HL case, which on review turned out to be HL/TCRBCL. Histopathological diagnosis was HL in all these nine cases. There were two histologically diagnosed TCRBCL cases during this period, with cytodiagnoses of NHL other than TCRBCL in one and HL in the other. While highlighting the difficulties associated with the cytodiagnosis of TCRBCL, this study conveys a word of caution that adequate immunocytochemical studies should be performed before diagnosing this rare neoplasm with a varied cytomorphology.     

Significance of C4d deposition in the follicular lymphoma and MALT lymphoma and their relationship with follicular dendritic cells

We evaluated the deposition of C4d in follicular lymphomas (FL) and extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Deposition of C4d was detected in 118 lymphoma tissues from patients with lymphoma and in 20 reactive hyperplasia lymphadens (RHL) using immunohistochemistical methods. FL, MALT lymphoma, and RHL were studied using double staining for CD35/C4d and Bcl-2/C4d. We studied 26 FL tissues, 19 of which showed C4d deposition. C4d deposition was detected around the follicular dendritic cells (FDCs) in the neoplastic follicles. There was no significant difference between the positive ratio of C4d and the grades of FL. We studied 12 MALT lymphoma tissues, six of which displayed C4d deposition. In these tissues, C4d deposition was detected in the peripheral region of partially colonized follicles in the form of an irregular ring, but was not found in the central region. C4d deposition was negative in completely colonized follicles. There was no C4d deposition in diffuse large B-cell lymphomas, mantle cell lymphomas, B-small lymphocytic lymphomas, T-lymphoblastic lymphomas, peripheral T-cell lymphomas, and anaplastic large cell lymphomas. C4d around the FDCs in the neoplastic follicles was a specific indicator for FL. C4d deposition in partially colonized follicles of MALT lymphoma was completely different from that in neoplastic follicles of FL, forming a key point for differential diagnosis.     

Malignant Lymphomas in the Head and Neck Region - a Retrospective,Single-Center Study over 41 Years

Objectives: Non-Hodgkin lymphomas are malignant neoplastic proliferations of the immune system that can manifest as nodal or extranodal lymphomas. The aim of this study was to retrospectively investigate the site of occurrence of lymphomas in the head and neck area and to analyze the typical symptoms of patients who presented at an oral and maxillofacial surgical department.Material and Methods: All patient files from1971 until 2012 from an Oral and Maxillofacial Surgery of a University were analyzed for the diagnosis non-Hodgkin lymphoma. Epidemiologic data and data regarding the localization of the malignant lymphoma were evaluated.Results: 62 patients, 34 women and 28 men with a non-Hodgkin lymphoma in the head and neck area were treated in the 41 years analyzed. In 87% of the cases the lymphoma belonged to B-cell and in 12% to the T-cell lineage. The average age at the time of diagnosis was 67 years for women (n=34) and 56 years for men. With 22 patients each, the non-Hodgkin lymphoma was localized in either the soft tissues or osseous structures. In the remaining 18 cases, multiple structures were affected. In 33 patients no accompanying nodal manifestation was noticed. In 33 cases the lymphoma was located in the oral cavity. The most common symptoms were swelling (97%), pain (40%) and the existence of an ulcer (11%).Conclusion: In the present study more than 50% of the lymphomas were located in the oral cavity. Due to the unspecific symptoms, a histopathological verification of the diagnosis is crucial.     

Primary Malignant Lymphoma of the Urinary Bladder A Case Report

A patient with primary malignant lymphoma of the urinary bladder is presented. Grossly, the bladder showed multiple submucosal masses. Histologically and immunohisto-chemically, diffuse B-cell lymphoma of the medium-sized cell type was revealed. On the basis of clinicopathological features, the present case resembled previously recorded cases of bladder lymphoma. The pathogenesis of this primary bladder lymphoma was presumably associated with follicular or chronic cystitis. Primary lymphoma of the bladder is a condition that is very rarely included in series of extranodal lymphomas, and there is a curious sex difference in its occurrence rates between Japan and Western countries. Primary lymphoma of the bladder may be considered a lymphoma that originates from mucosa associated lymphoid tissue. Acta Pathol Jpn 40: 764-769, 1990.