Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 4935
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

  Table of Contents    
Year : 2016  |  Volume : 59  |  Issue : 4  |  Page : 446-456
Plasmacytic or lymphoplasmacytic infiltrate in lymph nodes: Diagnostic approach and differential considerations

Department of Pathology, Duke University Medical Center, Durham, NC, USA

Click here for correspondence address and email

Date of Web Publication10-Oct-2016


Plasmacytosis is a common finding in lymph node biopsies and can be seen in diverse circumstances ranging from reactive lymphadenopathy to malignant lymphoma. Familiarity with various histopathologic features of the different entities and awareness of their typical clinical and ancillary study findings are essential for an accurate diagnosis. In this review, we present common and representative nonneoplastic entities and lymphomas that have plasmacytic differentiation or associated plasmacytosis. We focus on the histological classification with an emphasis on the diagnostic approach and areas of diagnostic challenge.

Keywords: Castleman disease, lymph node, lymphoplasmacytic lymphoma, mucosa-associated lymphoid tissue lymphoma, marginal zone lymphoma, plasmacytosis, primary effusion lymphoma, Rosai-Dorgman disease, syphilis, toxoplasma

How to cite this article:
Xie Y, Vallangeon B, Liu X, Lagoo AS. Plasmacytic or lymphoplasmacytic infiltrate in lymph nodes: Diagnostic approach and differential considerations. Indian J Pathol Microbiol 2016;59:446-56

How to cite this URL:
Xie Y, Vallangeon B, Liu X, Lagoo AS. Plasmacytic or lymphoplasmacytic infiltrate in lymph nodes: Diagnostic approach and differential considerations. Indian J Pathol Microbiol [serial online] 2016 [cited 2023 Nov 30];59:446-56. Available from:

   Introduction Top

A significant plasma cell/plasmacytoid cell component can occur in a variety of reactive and neoplastic lymph node disorders. Familiarity with the pathologic features of a diverse group of benign and malignant lymph node disorders is necessary to formulate the differential diagnosis, guide ancillary test selection and render a specific diagnosis. In this review, we first consider nonneoplastic entities that have a prominent or characteristic plasma cell infiltration and then examine lymphomas with plasmacytic differentiation or associated plasmacytosis. The simultaneous presence of neoplastic plasma cell infiltrate, and a lymphoma is a unique diagnostic challenge. We outline a basic approach to diagnosis using histologic patterns augmented by a limited number of ancillary studies and emphasize the potentially problematic and/or clinically significant differential diagnoses.

High-quality hematoxylin and eosin stained sections, preferably of intact and entirely excised lymph nodes, are essential. Prompt fixation of thin slices (<2 mm) of tissue in adequate quantities of buffered formalin offers optimal preservation of architectural and cytological details. Access to paraffin immunohistochemistry (IHC) for common hematolymphoid antigens is necessary. Flow cytometric examination to identify a clonal B-cell population at a minimum, and more extended immunophenotyping of the various lymphoid and related populations is very helpful in many cases. Molecular studies of immunoglobulin heavy chain (IgH) and T-cell receptor to establish clonality are sometimes necessary. Some noteworthy points regarding ancillary studies in this context - First, demonstrating the presence of clonal IgH by molecular studies cannot distinguish between clonal B-cells and clonal plasma cells, as can be done by flow cytometry. Second, IHC staining for kappa and lambda is usually not sensitive enough to determine clonality of B-cells, as it is for plasma cells. However, IHC stains for kappa and lambda and sometimes the IgHs may be helpful in evaluating potential lymphomas with plasmacytoid differentiation, such as marginal zone lymphoma (MZL) or lymphoplasmacytic lymphoma (LPL). [1] Finally, with IHC staining, a small number of monotypic plasma cells may be masked by the presence of more abundant polytypic, reactive plasma cells.

   Reactive Lymphadenopathies with Plasmacytic Infiltrate Top

Virtually, any compartment of the lymph node can be infiltrated by plasma cells in various types of benign lymphadenopathies. The number of plasma cells can vary from 1% to 2% to over 50% of total cells. It is helpful to group these entities based on the predominant plasma cell infiltration pattern: intrafollicular, interfollicular/paracortical, capsular and septal, and sinusoidal [Table 1]. It should be noted that multiple compartments can be involved in one process and the degree of involvement can be variable from case to case. Generally speaking in the reactive conditions, the nodal architecture may be disrupted, but usually not completely effaced; the plasma cells do not show significant cytologic atypia such as enlarged cells with central nuclei, fine chromatin, nucleoli, tri- or multi-nucleation, and Dutcher bodies; although, binucleation and Russell bodies can be seen. Demonstration of plasma cells/plasmacytoid cells by IHC and absence of clonal B cells by flow cytometry is helpful in excluding a neoplastic plasma cell or B cell process. However, it is important to keep in mind that light-chain restriction is not an absolute indicator of neoplasia. Nam-Cha et al. have described rare reactive lymphadenitis with light-chain-restricted plasma cells and plasmacytoid cells within germinal centers. These findings may be a manifestation of an underlying disorder in the regulation of the immune response or an exaggeration of the germinal center oligoclonal nature. [2]
Table 1: Plasma cell infiltration pattern in reactive lymphadenopathies

Click here to view

Autoimmune lymphadenopathy

Rheumatoid arthritis associated lymphadenopathy

Lymphadenopathy is frequently found in patients with autoimmune disorders such as rheumatoid arthritis (RA), Sjogren's syndrome, and systemic lupus erythematosus (SLE). [3],[4],[5] Because these patients have an increased risk of non-Hodgkin lymphoma, lymph node biopsy is sometimes performed when there is clinical suspicion of lymphoma. Histologically, RA-associated nonneoplastic lymphadenopathy typically shows reactive follicular hyperplasia and prominent interfollicular polytypic plasmacytosis. Plasma cells tend to also crowd into the germinal centers. The lymph node capsule is thickened but typically is not infiltrated by the plasma cells. The main differential diagnosis includes reactive follicular hyperplasia due to other causes. The clinical history and laboratory findings are helpful to confirm the diagnosis of RA-associated lymphadenopathy.

Systemic lupus erythematosus associated lymphadenopathy

The histologic features of lymph nodes in SLE are characterized by paracortical hyperplasia, often with foci of necrosis, resembling Kikuchi-Fujimoto disease. [5],[6] Plasma cells are present near the necrotic areas along with histiocytes, lymphocytes, immunoblasts, and abundant karyorrhectic debris. In contrast to Kikuchi-Fujimoto disease, neutrophils may be present and plasma cell infiltrate is more common. Hematoxylin bodies, which are collections of basophilic amorphous material composed of degenerated nuclei, are fairly specific, but not very sensitive feature of SLE and clinical correlation is generally necessary to definitively distinguish between SLE and Kikuchi-Fujimoto disease.

Infectious lymphadenopathy

Infectious mononucleosis

Infectious mononucleosis caused by acute Epstein-Barr virus (EBV) infection is usually asymptomatic in children; but lymph node and tonsillar biopsies are occasionally performed in adolescents and young adults, who are often symptomatic. Histologic features vary during the disease. [7] In the early stage, there is reactive follicular hyperplasia with monocytoid B-cell proliferation. [8] Later, there is an expansion of the paracortex by a polymorphous infiltrate consisting of immunoblasts, plasmacytoid cells, plasma cells, small lymphocytes, and histiocytes [Figure 1]. Necrosis may also be seen. Some cases may have nodules and sheets of immunoblasts with cytologic atypia, resembling large B-cell lymphoma. [7] In other cases, there are clusters of EBV + Reed-Sternberg-like cells, simulating classical Hodgkin lymphoma. [9] Morphologic features favoring infectious mononucleosis include the maintenance of the nodal architecture despite sometimes considerable distortion, the presence of both B and T-cell immunoblasts, a predominance of CD8+ T cells and the presence of both large and small EBV+ cells. [10],[11] Gene rearrangement studies may be useful; however, both immunoglobulin and T-cell receptor may show oligoclonal or occasionally monoclonal rearrangement patterns. [12]
Figure 1: Infectious mononucleosis. (a) Largely preserved nodal architecture with expanded paracortex (H and E, ×4). (b) Polymorphous paracortical infiltrate of large immunoblasts in a background of small to medium lymphocytes and plasma cells (H and E, ×20). (c) Lymphoid follicles and scattered interfollicular B cells seen with CD20 stain (CD20, ×10). (d) CD138 staining highlights abundant plasma cells in medullary sinuses (CD138, ×10). (e) B-immunoblasts in the interfollicular area (CD20, ×20). (f) CD3 staining highlights numerous T cells in the paracortex (CD3, ×20)

Click here to view

Cytomegalovirus associated lymphadenopathy

Cytomegalovirus (CMV) infection can clinically resemble infectious mononucleosis with localized or generalized lymphoadenopathy. [13] The involved lymph nodes often show reactive follicular hyperplasia, paracortical expansion with plasmacytoid cells, scattered immunoblasts, and monocytoid B-cell collections. Large cells containing prominent intranuclear and intracytoplasmic viral inclusions, mimicking Reed-Sternberg cells, may be found. [14] IHC stains using anti-CMV antibodies are helpful to confirm the diagnosis. [15]

Human immunodeficiency virus-associated lymphadenopathy

Persistent generalized lymphadenopathy is part of an HIV-related syndrome. The histologic picture of the lymph node varies in different stages of the disease. [16] In the early stage, follicles are often enlarged and the germinal centers may be irregular, serpentine or show follicle lysis, while in late stage, there is progressive lymphocyte depletion and follicles with regressive changes. Plasma cells can be seen in all stages, but they are more prominent in the interfollicular areas (paracortex) in the later stages.

Syphilitic (luetic) lymphadenopathy

Lymphadenopathy is regularly seen in primary and secondary syphilis and possibly in latent stage. There is typically follicular hyperplasia and often marked medullary and interfollicular plasmacytosis, reminiscent of autoimmune lymphadenopathy. [17] Features that point to luetic lymphadenitis include extensive capsular and trabecular fibrosis with infiltration by plasma cells, nonnecrotizing granulomas with epithelioid histiocytes and giant cells, and endarteritis and venulitis. [18] The diagnosis can be confirmed by the detection of Treponema pallidum, IHC and PCR testing being more sensitive than silver staining. [19]

Infectious granulomatous lymphadenitis

A wide variety of infectious etiology, such as fungal infections, toxoplasmosis [Figure 2], tuberculosis, atypical mycobacterial disease, pneumoconiosis, can cause granulomatous lymphadenitis and show significant plasma cell infiltration. Infectious granulomatous lymphadenitis can be classified into suppurative and nonsuppurative lymphadenitis. Primary etiology can be established by special stain or immunostain, and can be confirmed by serologic assays, microbial culture, and molecular methods. [20]
Figure 2, Toxoplasma lymphadenitis. (a) reactive follicles and clusters of epithelioid histiocytes within the germinal centers (H and E, ×2). (b) Plasma cells in the interfollicular area and epithelioid histiocytes in germinal center (H and E, ×20)

Click here to view

Lymphadenopathy of unclear etiology

Castleman's disease

Castleman's disease (CD) is an uncommon disorder first described by Castleman and Towne as a localized mediastinal lymph node hyperplasia resembling thymoma. [21],[22] Clinically, CD can be classified as the unicentric or multicentric type and pathologically as hyaline vascular or plasma cell variant. [23] Hyaline vascular CD, the most common CD, usually presents as a localized mass and is characterized by small follicles associated with hyalinized vessels and interfollicular capillary proliferation, but a variable number of plasma cells are almost always present in interfollicular areas [Figure 3]a and b. Plasma cell variant CD features hyperplastic or small regressed follicles with moderate to extensive sheets of plasma cells in between [Figure 3]c and d. The plasma cells are generally polytypic in CD, but may be monoclonal in some plasma cell variant CD, usually with lambda light-chain restriction. The majority express IgG, and a small subset expresses IgA. [24],[25] Lambda light-chain restriction can also be demonstrated in a proportion of HIV + patients with human herpesvirus 8-positive multicentric CD (HHV8 MCD). [26] In these cases, there may be variable numbers of large immature plasma cells, i.e., plasmablasts, present in the mantle zones, expressing intranuclear HHV8 latency-associated nuclear antigen, viral interleukin-6 (IL-6) and cIgM with lambda light-chain restriction. [27] Despite a monotypic staining pattern, molecular studies have shown that these cells constitute a polyclonal population. [28] Whether such cases transform into an HHV8-positive plasmablastic lymphoma (PBL) is controversial. [29]
Figure 3: Castleman disease and Rosai-Dorfman disease. Hyaline-vascular Castleman disease. (a) Follicles with expanded mantle zones and multiple atrophic germinal centers in a single mantle zone (H and E, ×4). (b) Germinal center penetrated by a hyalinized vessel. Scattered plasma cells are seen in the interfollicular areas (H and E, ×20). Plasma cell variant Castleman disease. (c) Follicular hyperplasia and marked interfollicular plasmacytosis (H and E, ×4). (d) Numerousplasma cells in perifollicular area (H and E, ×20). Rosai-Dorfman disease. (e) Collections of plump histiocytes and lymphoplasmacytic cells (H and E, ×20). (f) The histiocytes have large round nuclei and prominent nucleoli. Note the emperipolesis of lymphocytes and plasma cells (H and E, ×40)

Click here to view

IgG4 related disease

Lymphadenopathy of IgG4 related disease can exhibit a broad morphologic spectrum, including MCD-like, follicular hyperplasia, interfollicular expansion, progressive transformation of germinal centers (PTGC), and inflammatory pseudotumor (IPT)-like. [30],[31] While the morphologic features are nonspecific, one characteristic IHC finding in all is the presence of abundant IgG4+ plasma cells (>100 IgG4+ plasma cells per high power field and IgG4/IgG ratio >40%). IgG4+ plasma cells are often found in both the germinal centers and interfollicular zone, although they are located predominantly within germinal centers for PTGC pattern. In only a subset of the IgG4-related lymphadenopathy, particularly the IPT-like type, there is storiform fibrosis with intermingled lymphocytes and plasma cells, which is a characteristic morphologic feature seen in IgG4-related disease in extranodal sites. It must be kept in mind that an increase of IgG4+ cells and IgG4/IgG ratio is not very specific and has been reported in other reactive and neoplastic conditions, including Rosai-Dorfman disease and MZL etc. [32],[33] Clinical and laboratory findings must be taken into consideration to reach a diagnosis of IgG4-related disease.

Rosai-Dorfman disease

Plasma cells are typically numerous in this indolent histiocytic disorder of unknown etiology, in which increased histiocytes occur in the sinus and paracortex, with an S-100+/CD68+/CD4+ immunophenotype and prominent emperipolesis (presence of lymphocytes, plasma cells, and occasionally other cells in their cytoplasm). [34] Variable numbers of plasma cells are present in the interfollicular and paracortical areas in almost all cases [Figure 3]e and f.

Inflammatory pseudotumor

IPT is an uncommon reactive condition of lymph nodes characterized by proliferation of the myofibroblastic cells, small vessels, and mixed inflammatory cells including lymphocytes and plasma cells as well as occasional eosinophils and neutrophils. [35] While the pathogenesis of IPT has remained obscure, the absence of anaplastic lymphoma kinase (ALK) expression in all cases of IPT of the lymph node indicates that this entity is biologically distinct from the inflammatory myofibroblastic tumors found in soft tissue. [36]

   Small B-Cell Lymphomas with Plasmacytic Differentiation Top

Plasmacytic or plasmacytoid differentiation can be found in a variety of small B-cell lymphomas, including MZL, LPL, chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), follicular lymphoma (FL), mantle cell lymphoma, etc., Flow cytometric demonstration of monotypic B-cells with characteristic immunophenotype is helpful in many cases, but the distinction between some LPLs and MZLs can be very challenging because they share overlapping morphologic and immunophenotypic features. [37] It usually requires the integration of clinical history, morphology, immunophenotype, and molecular/cytogenetic analysis to achieve a definitive diagnosis. In certain cases, only a descriptive diagnosis of "small B-cell lymphoma with plasmacytic differentiation" is possible. In cases with a predominant plasma cell component, the possibility of a coexisting plasma cell neoplasm also needs to be ruled out. [38]

Nodal marginal zone lymphoma

Nodal MZL (NMZL) is a rare indolent B-cell lymphoma mainly affecting older adults (median age 60 years). [39],[40] It often presents with Stage III or IV disease, sometimes with B symptoms. [41],[42],[43] Variable morphologic patterns (diffuse, perifollicular, interfollicular, and nodular) are recognized, characterized by heterogeneous proliferation including marginal zone B cells (centrocyte-like, monocytoid), plasmacytoid cells, plasma cells, and scattered transformed B-cells (centroblasts and immunoblasts). [44],[45] Plasmacytoid differentiation is common and can be extensive. [46],[47] Dutcher and Russel bodies may be seen. The residual follicles can be expanded, regressed, or colonized by neoplastic cells [Figure 4]. NMZLs express pan-B-cell markers including CD20, CD79a, and PAX5. The majority of cases lack CD5, CD23, CD10, and BCL6, although expression of these markers has been reported. In most cases, BCL2 is weakly expressed and in up to 50% of cases, CD43 is positive. Cells with plasmacytic/plasmacytoid differentiation are positive for MUM1. In addition, cytoplasmic immunoglobulin expression can often be detected. They are mostly IgM+, rarely IgG+ or IgA+. Identification of light-chain restriction by flow cytometry favors a lymphomatous process. However, some cases of reactive marginal zone hyperplasia, particularly in pediatric patients, can show lambda light-chain restriction even though they are polyclonal by molecular analysis. [48] The differential diagnosis of NMZL frequently includes other low-grade B-cell lymphomas with plasmacytic differentiation and plasma cell neoplasms. These entities are discussed further in the following sections.
Figure 4: Nodal marginal zone lymphoma. (a) Pale staining, "monocytoid" lymphoid cells expand the interfollicular areas and focally infiltrate the follicles (H and E, ×2). (b) A rim of clear cytoplasm imparts the monocytoid appearance. Few Dutcher bodies are present (H and E, ×40). (c) CD20 highlights abundant B cells in the interfollicular areas (CD20, ×20). (d) Plasmacytoid B-cells and plasma cells are positive for MUM1 (MUM1, ×20). (e) These cells show kappa light-chain restriction (Kappa, ×20). (f) Lambda is negative in these cells. Note the scattered reactive plasma cells (Lambda, ×20)

Click here to view

Lymphoplasmacytic lymphoma

LPL usually involves bone marrow, less commonly involving extramedullary sites such as lymph nodes and spleen. It is composed of small B lymphocytes, plasmacytoid lymphocytes, and plasma cells. In most instances, LPL is associated with an IgM paraprotein, resulting in Waldenstrom macroglobulinemia (WM) (defined as an LPL with bone marrow involvement and any level of an IgM monoclonal gammopathy). [37] It should be noted that IgM paraprotein can also occur in other B-cell neoplasms (e.g., MZLs), or as IgM producing monoclonal gammapathy of underdetermined significance (MGUS) and rarely as IgM myeloma.

Lymph nodes involved by LPL typically show subtle paracortical expansion, sparing the lymph node sinuses. Lymphoid follicles are often regressed, but follicular colonization can be seen. Compared to NMZL, the infiltrate is more uniform, containing a relatively monotonous population of small lymphocytes, plasmacytoid lymphocytes, and varying numbers of plasma cells [Figure 5]. Dutcher bodies are common. In addition, prominent mast cells and hemosiderin deposition may be present. [37],[49]
Figure 5: Lymphoplasmacytic lymphoma. (a) Histologic picture of lymphoplasmacytic lymphoma. The nodal architecture is replaced by a dense lymphoplasmacytic infiltrate (H and E, ×2). (b) Higher magnification view of lymphoplasmacytic lymphoma. Note the abundant plasmacytoid lymphocytes in the infiltrate (H and E, ×40). (c) The plasmacytoid lymphocytes are positive for CD20, (CD20, ×4). (d) MUM1 staining of the same area. The plasmacytoid lymphocytes are MUM1+ (MUM1, ×4)

Click here to view

The B lymphocytes in LPL are typically negative for CD5, CD10 and CD23, although variable expression can be seen in some cases (5-50%). [37],[50] LPL plasma cells are positive for CD138, CD38, CD19, and CD45 and they exhibit the same cytoplasmic light-chain restriction as the corresponding surface light-chain-restricted B lymphocytes. Recent studies demonstrate that PAX5 coexpression by CD138+ plasma cells is more common in LPL/WM than in plasma cell myeloma (PCM) or MZL, indicating the aberrant persistence of the B-cell transcriptional program in LPL/WM plasma cells. [51]

The IGH/PAX5 (t(9;14)) translocation is no longer considered sensitive or specific for LPL, but 6q21 deletion, although nonspecific, is reported in up to 63% of bone marrow based LPL/WM cases [52],[53] and is useful in discriminating WM from IgM MGUS. [52] Notably, it is neither a prognostic marker nor a characteristic marker for nodal LPL. [37],[54]

Recently, the use of whole-genome sequencing has helped to identify a highly recurrent somatic mutation, myeloid differentiation primary response factor 88 (MYD88) L265P in >90% of LPL/WM. [55] The mutation has also been found in a subset of IgM MGUS and diffuse large B-cell lymphoma (DLBCL), but much less frequently in other small B-cell neoplasms, such as nodal or extranodal MZL, splenic MZL, and CLL as well as hairy cell leukemia and PCM. Subsequent studies from multiple institutions have demonstrated that detection of the MYD88 L265P mutation can assist in classifying challenging bone-marrow and nodal small B-cell neoplasms with plasmacytic differentiation in routine practice. [56],[57]

Follicular lymphoma with plasmacytic differentiation

On occasion, FLmay show marginal zone or plasmacytic differentiation. [58],[59],[60] The degree of plasmacytic differentiation varies among cases, ranging from easily recognized mature plasma cells to the more common plasmacytoid cells. In a small number of cases, plasmacytic differentiation is only identified by IHC stain. [61] The number of plasma cells varies greatly, from few scattered cells to sheet-like collections, and the plasmacytic population may demonstrate a predominantly interfollicular, intrafollicular or perifollicular distribution.

One study analyzed 14 well-characterized FLs with plasmacytic differentiation and demonstrated the presence of the same cytogenetic abnormality in both the plasmacytic (CD138+) and nonplasmacytic (CD138-) component. [62] Furthermore, the presence of BCL2 translocation in plasma cells was strongly associated with a predominantly interfollicular plasma cell distribution. Conversely, the absence of a BCL2 translocation was associated with a prominent intra/perifollicular plasma cell population. These findings indicate that the latter cases may be distinctive, sharing some features with MZLs. [62]

Small lymphocytic lymphoma/chronic lymphocytic leukemia with plasmacytic differentiation

CLL/SLL is most frequently diagnosed by examination of blood. Despite the common nature of SLL/CLL, cases of true CLL/SLL with definitive plasmacytic differentiation are very rare. Evans et al. reported one rare case of CD5-positive CLL/SLL with focal striking plasmacytic differentiation in the lymph node. [63] Interestingly, plasma cells, which expressed membrane CD5, were not identified in the peripheral blood or bone marrow. This case was also unusual for the presence of an abnormality of chromosome 1p36, which is commonly seen in other types of B-cell lymphoma but not in CLL/SLL.

If there is prominent plasma cell differentiation, differentiating SLL/CLL from LPL, may require demonstration of characteristic cytogenetic abnormalities of CLL (trisomy 12, deletion 13q14, deletion 11q22-33, and deletion 17q13) and absence of MYD88 mutation. [63],[64] Lymphocyte enhancer-binding factor 1 is another useful marker for SLL/CLL in difficult or equivocal cases, and 10% positivity of the tumor cells is suggested to make more robust diagnosis of SLL/CLL. [65]

   Plasma Cell Neoplasms Involving the Lymph Node Top

Most plasma cell neoplasms originate as bone marrow tumors; however, the extramedullary disease can occasionally occur. Lymph node involvement can be a manifestation of advanced disease in PCM, regional lymph node involvement in extramedullary plasmacytoma (EMP) or even more rarely as a primary lymph nodal plasmacytoma (PLNP).

Extramedullary plasmacytoma

The histologic features of PLNP and other EMPs are similar. In most cases, the lymph node architecture is effaced by a diffuse proliferation of plasma cells. Occasionally, an interfollicular infiltration by monoclonal plasma cells is present [Figure 6]. The plasma cells are mostly of small mature Marschalko type, [66] but rare cases may demonstrate immature or pleomorphic plasma cells [Figure 7]c. Intracellular Ig may produce Dutcher bodies, Russell bodies, and crystalline rods.
Figure 6: Plasmacytoma. (a) Histologic picture of plasmacytoma. Note the diffuse proliferation of mature appearing plasma cells (H and E, ×20). (b) Immunostaining for CD20 highlights the residual follicles (CD20, ×20). (c) Immunostaining for CD138 highlights the neoplastic plasma cells (CD138, ×20)

Click here to view
Figure 7: Plasmablastic lymphoma, extracavitary primary effusion lymphoma and plasma cell myeloma with plasmablastic morphology. Higher magnification view of plasmablastic lymphoma (a; H and E, ×40), extracavitary primary effusion lymphoma (b; H and E, ×40) and plasma cell myeloma with plasmablastic morphology (c; H and E, ×40). Note the overlapping cytologic features

Click here to view

Lymph node involvement by advanced stage PCM and by EMP cannot be distinguished on a morphologic basis alone, although there seem to be diagnostically useful immunophenotypic differences. Whereas extramedullary involvement in advanced stage PCM is frequently CD56+ and not infrequently CD117+, cyclin D1+ or p53+, EMPs are rarely positive for these markers. [67] The distinction of nodal plasmacytoma from MZL and LPL with extensive plasmacytoid differentiation may require demonstration of clonal B-cells by flow cytometry.

Heavy-chain disease

Heavy-chain diseases (HCDs) are a rare group of B-cell neoplasms characterized by an excessive production of incomplete heavy chains, without associated light chains. Depending on the subtype of the altered heavy chain, the HCDs are subclassified as alpha, gamma, or mu HCD. [68] Each HCD demonstrates unique clinicopathological features:-Alpha HCD is the commonest type and is considered to be a variant of mucosa-associated lymphoid tissue lymphoma lymphoma, typically involving gastrointestinal tract and mesenteric lymph nodes. Gamma HCD most frequently presents as a lymphoplasmacytic proliferation in lymph nodes and extranodal tissue, resembling LPL. Mu HCD is rare and typically involves blood and bone marrow, resembling CLL. [69] Serum protein electrophoresis may not show a characteristic monoclonal spike, and immunofixation electrophoresis is often needed to establish the diagnosis.

   Large B-Cell Lymphomas with Plasmacytic/Plasmablastic Differentiation Top

These tumors show cytologic and/or immunophenotypic features of plasma cells or plasmablasts and can be broadly divided into two groups - those showing loss of most pan-B-cell antigens and those retaining the mature B-cell phenotype. Among the former group, PBL, ALK-positive DLBCL, primary effusion lymphoma (PEL) and extracavitary PEL, and EMP tumors secondary to multiple myeloma or plasmacytoma deserve attention. The clinicopathological properties of these entities are summarized in [Table 2] and representative cases are illustrated in [Figure 7].
Table 2: Large B - cell lymphomas with plasmacytic/plasmablastic differentiation

Click here to view

Other large B-cell lymphomas which may demonstrate plasmacytic differentiation but maintain a mature B-cell phenotype include PBL associated with MCD, DLBCL with secretory differentiation, pyothorax-associated lymphomas, and atypical Burkitt lymphoma with plasmacytic differentiation. [89] PBL associated with MCD is a somewhat controversial disease entity in which HHV-8 positive plasmablasts with light-chain restriction (typically lambda IgM) coalesce within the mantle zones to form either small confluent clusters or large lymphomatous sheets. [27] Pyothorax-associated lymphoma is a distinct entity among DLBCLs which present with recurrent pyothorax and may be regarded as an EBV-associated lymphoma derived from postgerminal center/activated B-cells. [90] Burkitt lymphoma is an aggressive B-cell lymphoma characterized by a translocation between the MYC gene and the IGH gene. Those with plasmacytic differentiation tend to occur in association with immunodeficiency and show monotypic cytoplasmic immunoglobulin. [91]

   T-Cell Lymphoma with Increased Plasma Cells Top

The T-cell lymphoma likely to show increased plasma cells in the lymph node biopsy is angioimmunoblastic T-cell lymphoma (AITL), the second most common peripheral T-cell lymphoma. The B-cell expansion in this lymphoma is thought to be related to the function of the neoplastic cells as T-follicular helper cells, while the known association of EBV infection of the B cells and increased release of cytokines, such IL-6 or IL-10 may contribute to the plasma cell proliferation in AITL. In a subset of the cases, monoclonal B cell or plasma cell proliferation can be detected. As demonstrated by Huppmann et al. (2013), the B-cell or plasma cell expansion in AITL can be so great, as to partially overshadow or obscure the underlying T-cell neoplasm. [92] Awareness of this eventuality is important to avoid misdiagnosis and inappropriate therapy.

Diagnostic approach for lymph node biopsies with a prominent plasma cell infiltrate

In the evaluation of lymph node biopsies with increased plasma cells or plasmacytoid cells, often the initial step is to differentiate reactive lymph nodes from a lymphomatous process. There are probably two key points that the pathologist should consider. First, is the lymph node architecture effaced or intact? Second, is there evidence of clonal B-cell or plasma-cell expansion? Several pathologic features favor a reactive lymph node: largely preserved nodal architecture; lack of significant cytologic atypia; and lack of monoclonal B-cell or plasma cell population. Ancillary studies such as flow cytometry and IHC are often employed to evaluate B-cell and plasma cell clonality. It is important to be aware that light-chain restriction is not an absolute indicator of neoplasia. In some reactive conditions, such as KSHV-positive MCD, the B cells/plasma cells are monotypic but polyclonal.

Depending on the extent of the involvement, small B-cell lymphomas may show effaced or largely preserved nodal architecture. Distinguishing among the various small B-cell lymphomas, such as NMZL, LPL and sometimes atypical CLL, can be difficult because of overlapping morphologic and immunophenotypic features. Cytogenetic and molecular study, such as MYD88 L265P mutation analysis, has proven to be a useful adjunct in the diagnosis of LPL and small B-cell lymphoma mimics. [3],[4] While the presence of B-cell and plasma-cell populations with the same light-chain restriction is an important clue to the B-cell lymphoma with plasmacytic differentiation, it must be remembered that finding identical light chains is not definitive evidence of clonal identity, and the possibility of a composite plasma cell neoplasm needs to be ruled out.

When large B-cell lymphomas develop significant plasmacytic differentiation, they often lose mature B-cell-associated antigens such as CD20 and PAX-5 and gain expression of plasma cell markers such as EMA, CD138, and CD38. They may aberrantly express T cell markers, and EBV and/or HHV8 may be positive. It often is challenging to differentiate PBL and the plasmablastic variant of PCM on the basis of the morphologic examination alone. However, the patient's demographics, clinical history, and bone marrow findings may strongly suggest a particular diagnosis.

   Summary Top

In summary, plasmacytosis is a common finding in lymph node specimen and can be seen in diverse circumstances including reactive lymphadenopathy, small B-cell lymphomas, large B-cell lymphomas, plasma cell neoplasms, and even T-cell lymphomas. It is important to consider a wide differential diagnosis. A systematic approach combined with appropriate histopathologic findings and ancillary test selection may help to formulate the differential diagnosis and ultimately to render a correct diagnosis. Molecular and cytogenetic studies are helpful in arriving at a specific diagnosis in morphologically challenging cases. It is important to remember that the ancillary studies must always be interpreted in the context of the clinical settings and histopathologic features.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Garcia CF, Swerdlow SH. Best practices in contemporary diagnostic immunohistochemistry: Panel approach to hematolymphoid proliferations. Arch Pathol Lab Med 2009;133:756-65.  Back to cited text no. 1
Nam-Cha SH, San-Millán B, Mollejo M, García-Cosio M, Garijo G, Gomez M, et al. Light-chain-restricted germinal centres in reactive lymphadenitis: Report of eight cases. Histopathology 2008;52:436-44.  Back to cited text no. 2
Kondratowicz GM, Symmons DP, Bacon PA, Mageed RA, Jones EL. Rheumatoid lymphadenopathy: A morphological and immunohistochemical study. J Clin Pathol 1990;43:106-13.  Back to cited text no. 3
McCurley TL, Collins RD, Ball E, Collins RD. Nodal and extranodal lymphoproliferative disorders in Sjogren's syndrome: A clinical and immunopathologic study. Hum Pathol 1990;21:482-92.  Back to cited text no. 4
Eisner MD, Amory J, Mullaney B, Tierney L Jr., Browner WS. Necrotizing lymphadenitis associated with systemic lupus erythematosus. Semin Arthritis Rheum 1996;26:477-82.  Back to cited text no. 5
Medeiros LJ, Kaynor B, Harris NL. Lupus lymphadenitis: Report of a case with immunohistologic studies on frozen sections. Hum Pathol 1989;20:295-9.  Back to cited text no. 6
Childs CC, Parham DM, Berard CW. Infectious mononucleosis. The spectrum of morphologic changes simulating lymphoma in lymph nodes and tonsils. Am J Surg Pathol 1987;11:122-32.  Back to cited text no. 7
Anagnostopoulos I, Hummel M, Falini B, Joehrens K, Stein H. Epstein-barr virus infection of monocytoid B-cell proliferates: An early feature of primary viral infection? Am J Surg Pathol 2005;29:595-601.  Back to cited text no. 8
Abbondanzo SL, Sato N, Straus SE, Jaffe ES. Acute infectious mononucleosis. CD30 (Ki-1) antigen expression and histologic correlations. Am J Clin Pathol 1990;93:698-702.  Back to cited text no. 9
Niedobitek G, Herbst H, Young LS, Brooks L, Masucci MG, Crocker J, et al. Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue. Blood 1992;79:2520-6.  Back to cited text no. 10
Kojima M, Nakamura S, Itoh H, Yoshida K, Suchi T, Masawa N. Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma. A clinicopathological study of nine cases. APMIS 2001;109:419-27.  Back to cited text no. 11
Weiss LM, O'Malley D. Benign lymphadenopathies. Mod Pathol 2013;26 Suppl 1:S88-96.  Back to cited text no. 12
Klemola E, Kääriäinen L. Cytomegalovirus as a possible cause of a disease resembling infectious mononucleosis. Br Med J 1965;2:1099-102.  Back to cited text no. 13
Tindle BH, Parker JW, Lukes RJ. "Reed-Sternberg cells" in infectious mononucleosis? Am J Clin Pathol 1972;58:607-17.  Back to cited text no. 14
Abramowitz A, Livni N, Morag A, Ravid Z. An immunoperoxidase study of cytomegalovirus mononucleosis. Arch Pathol Lab Med 1982;106:115-8.  Back to cited text no. 15
Houn HY, Pappas AA, Walker EM Jr. Lymph node pathology of acquired immunodeficiency syndrome (AIDS). Ann Clin Lab Sci 1990;20:337-42.  Back to cited text no. 16
Hartsock RJ, Halling LW, King FM. Luetic lymphadenitis: A clinical and histologic study of 20 cases. Am J Clin Pathol 1970;53:304-14.  Back to cited text no. 17
Farhi DC, Wells SJ, Siegel RJ. Syphilitic lymphadenopathy. Histology and human immunodeficiency virus status. Am J Clin Pathol 1999;112:330-4.  Back to cited text no. 18
Behrhof W, Springer E, Bräuninger W, Kirkpatrick CJ, Weber A. PCR testing for Treponema pallidum in paraffin-embedded skin biopsy specimens: Test design and impact on the diagnosis of syphilis. J Clin Pathol 2008;61:390-5.  Back to cited text no. 19
Asano S. Granulomatous lymphadenitis. J Clin Exp Hematop 2012;52:1-16.  Back to cited text no. 20
Castleman B, Towne VW. Case records of the Massachusetts general hospital: Case No 40231. N Engl J Med 1954;250:1001-5.  Back to cited text no. 21
Castleman B, Iverson L, Menendez VP. Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer 1956;9:822-30.  Back to cited text no. 22
Frizzera G. Castleman's disease and related disorders. Semin Diagn Pathol 1988;5:346-64.  Back to cited text no. 23
Radaszkiewicz T, Hansmann ML, Lennert K. Monoclonality and polyclonality of plasma cells in Castleman's disease of the plasma cell variant. Histopathology 1989;14:11-24.  Back to cited text no. 24
Hall PA, Donaghy M, Cotter FE, Stansfeld AG, Levison DA. An immunohistological and genotypic study of the plasma cell form of Castleman's disease. Histopathology 1989;14:333-46.  Back to cited text no. 25
Menke DM, Tiemann M, Camoriano JK, Chang SF, Madan A, Chow M, et al. Diagnosis of Castleman's disease by identification of an immunophenotypically aberrant population of mantle zone B lymphocytes in paraffin-embedded lymph node biopsies. Am J Clin Pathol 1996;105:268-76.  Back to cited text no. 26
Dupin N, Diss TL, Kellam P, Tulliez M, Du MQ, Sicard D, et al. HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma. Blood 2000;95:1406-12.  Back to cited text no. 27
Du MQ, Liu H, Diss TC, Ye H, Hamoudi RA, Dupin N, et al. Kaposi sarcoma-associated herpesvirus infects monotypic (IgM lambda) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders. Blood 2001;97:2130-6.  Back to cited text no. 28
Xie Y, Pittaluga S, Jaffe ES. The histological classification of diffuse large B-cell lymphomas. Semin Hematol 2015;52:57-66.  Back to cited text no. 29
Cheuk W, Chan JK. Lymphadenopathy of IgG4-related disease: An underdiagnosed and overdiagnosed entity. Semin Diagn Pathol 2012;29:226-34.  Back to cited text no. 30
Cheuk W, Yuen HK, Chu SY, Chiu EK, Lam LK, Chan JK. Lymphadenopathy of IgG4-related sclerosing disease. Am J Surg Pathol 2008;32:671-81.  Back to cited text no. 31
Menon MP, Evbuomwan MO, Rosai J, Jaffe ES, Pittaluga S. A subset of Rosai-Dorfman disease cases show increased IgG4-positive plasma cells: Another red herring or a true association with IgG4-related disease? Histopathology 2014;64:455-9.  Back to cited text no. 32
Venkataraman G, Rizzo KA, Chavez JJ, Streubel B, Raffeld M, Jaffe ES, et al. Marginal zone lymphomas involving meningeal dura: Possible link to IgG4-related diseases. Mod Pathol 2011;24:355-66.  Back to cited text no. 33
Eisen RN, Buckley PJ, Rosai J. Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Semin Diagn Pathol 1990;7:74-82.  Back to cited text no. 34
Davis RE, Warnke RA, Dorfman RF. Inflammatory pseudotumor of lymph nodes. Additional observations and evidence for an inflammatory etiology. Am J Surg Pathol 1991;15:744-56.  Back to cited text no. 35
Kutok JL, Pinkus GS, Dorfman DM, Fletcher CD. Inflammatory pseudotumor of lymph node and spleen: An entity biologically distinct from inflammatory myofibroblastic tumor. Hum Pathol 2001;32:1382-7.  Back to cited text no. 36
Lin P, Molina TJ, Cook JR, Swerdlow SH. Lymphoplasmacytic lymphoma and other non-marginal zone lymphomas with plasmacytic differentiation. Am J Clin Pathol 2011;136:195-210.  Back to cited text no. 37
Alley CL, Wang E, Dunphy CH, Gong JZ, Lu CM, Boswell EL, et al. Diagnostic and clinical considerations in concomitant bone marrow involvement by plasma cell myeloma and chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis: A series of 15 cases and review of literature. Arch Pathol Lab Med 2013;137:503-17.  Back to cited text no. 38
Berger F, Felman P, Thieblemont C, Pradier T, Baseggio L, Bryon PA, et al. Non-MALT marginal zone B-cell lymphomas: A description of clinical presentation and outcome in 124 patients. Blood 2000;95:1950-6.  Back to cited text no. 39
Nathwani BN, Anderson JR, Armitage JO, Cavalli F, Diebold J, Drachenberg MR, et al. Marginal zone B-cell lymphoma: A clinical comparison of nodal and mucosa-associated lymphoid tissue types. Non-Hodgkin's lymphoma classification project. J Clin Oncol 1999;17:2486-92.  Back to cited text no. 40
Kojima M, Inagaki H, Motoori T, Itoh H, Shimizu K, Tamaki Y, et al. Clinical implications of nodal marginal zone B-cell lymphoma among Japanese: Study of 65 cases. Cancer Sci 2007;98:44-9.  Back to cited text no. 41
Oh SY, Ryoo BY, Kim WS, Kim K, Lee J, Kim HJ, et al. Nodal marginal zone B-cell lymphoma: Analysis of 36 cases. Clinical presentation and treatment outcomes of nodal marginal zone B-cell lymphoma. Ann Hematol 2006;85:781-6.  Back to cited text no. 42
Traverse-Glehen A, Felman P, Callet-Bauchu E, Gazzo S, Baseggio L, Bryon PA, et al. A clinicopathological study of nodal marginal zone B-cell lymphoma. A report on 21 cases. Histopathology 2006;48:162-73.  Back to cited text no. 43
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.  Back to cited text no. 44
van den Brand M, van Krieken JH. Recognizing nodal marginal zone lymphoma: Recent advances and pitfalls. A systematic review. Haematologica 2013;98:1003-13.  Back to cited text no. 45
Davis GG, York JC, Glick AD, McCurley TL, Collins RD, Cousar JB. Plasmacytic differentiation in parafollicular (monocytoid) B-cell lymphoma. A study of 12 cases. Am J Surg Pathol 1992;16:1066-74.  Back to cited text no. 46
Salama ME, Lossos IS, Warnke RA, Natkunam Y. Immunoarchitectural patterns in nodal marginal zone B-cell lymphoma: A study of 51 cases. Am J Clin Pathol 2009;132:39-49.  Back to cited text no. 47
Attygalle AD, Liu H, Shirali S, Diss TC, Loddenkemper C, Stein H, et al. Atypical marginal zone hyperplasia of mucosa-associated lymphoid tissue: A reactive condition of childhood showing immunoglobulin lambda light-chain restriction. Blood 2004;104:3343-8.  Back to cited text no. 48
Tournilhac O, Santos DD, Xu L, Kutok J, Tai YT, Le Gouill S, et al. Mast cells in Waldenstrom's macroglobulinemia support lymphoplasmacytic cell growth through CD154/CD40 signaling. Ann Oncol 2006;17:1275-82.  Back to cited text no. 49
Hunter ZR, Branagan AR, Manning R, Patterson CJ, Santos DD, Tournilhac O, et al. CD5, CD10, and CD23 expression in Waldenstrom's macroglobulinemia. Clin Lymphoma 2005;5:246-9.  Back to cited text no. 50
Roberts MJ, Chadburn A, Ma S, Hyjek E, Peterson LC. Nuclear protein dysregulation in lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia. Am J Clin Pathol 2013;139:210-9.  Back to cited text no. 51
Schop RF, Van Wier SA, Xu R, Ghobrial I, Ahmann GJ, Greipp PR, et al. 6q deletion discriminates Waldenström macroglobulinemia from IgM monoclonal gammopathy of undetermined significance. Cancer Genet Cytogenet 2006;169:150-3.  Back to cited text no. 52
Schop RF, Kuehl WM, Van Wier SA, Ahmann GJ, Price-Troska T, Bailey RJ, et al. Waldenström macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions. Blood 2002;100:2996-3001.  Back to cited text no. 53
Cook JR, Aguilera NI, Reshmi S, Huang X, Yu Z, Gollin SM, et al. Deletion 6q is not a characteristic marker of nodal lymphoplasmacytic lymphoma. Cancer Genet Cytogenet 2005;162:85-8.  Back to cited text no. 54
Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. N Engl J Med 2012;367:826-33.  Back to cited text no. 55
Ondrejka SL, Lin JJ, Warden DW, Durkin L, Cook JR, Hsi ED. MYD88 L265P somatic mutation: Its usefulness in the differential diagnosis of bone marrow involvement by B-cell lymphoproliferative disorders. Am J Clin Pathol 2013;140:387-94.  Back to cited text no. 56
Hamadeh F, MacNamara SP, Aguilera NS, Swerdlow SH, Cook JR. MYD88 L265P mutation analysis helps define nodal lymphoplasmacytic lymphoma. Mod Pathol 2015;28:564-74.  Back to cited text no. 57
Vago JF, Hurtubise PE, Redden-Borowski MM, Martelo OJ, Swerdlow SH. Follicular center-cell lymphoma with plasmacytic differentiation, monoclonal paraprotein, and peripheral blood involvement. Recapitulation of normal B-cell development. Am J Surg Pathol 1985;9:764-70.  Back to cited text no. 58
Schmid U, Karow J, Lennert K. Follicular malignant non-Hodgkin's lymphoma with pronounced plasmacytic differentiation: A plasmacytoma-like lymphoma. Virchows Arch A Pathol Anat Histopathol 1985;405:473-81.  Back to cited text no. 59
Frizzera G, Anaya JS, Banks PM. Neoplastic plasma cells in follicular lymphomas. Clinical and pathologic findings in six cases. Virchows Arch A Pathol Anat Histopathol 1986;409:149-62.  Back to cited text no. 60
Gradowski JF, Jaffe ES, Warnke RA, Pittaluga S, Surti U, Gole LA, et al. Follicular lymphomas with plasmacytic differentiation include two subtypes. Mod Pathol 2010;23:71-9.  Back to cited text no. 61
Goodlad JR, Batstone PJ, Hamilton D, Hollowood K. Follicular lymphoma with marginal zone differentiation: Cytogenetic findings in support of a high-risk variant of follicular lymphoma. Histopathology 2003;42:292-8.  Back to cited text no. 62
Evans HL, Polski JM, Deshpande V, Dunphy CH. CD5+ true SLL/CLL with plasmacytic differentiation and an unusual 1p36 translocation: Case report and review of the literature. Leuk Lymphoma 2000;39:625-32.  Back to cited text no. 63
Rossi D. Role of MYD88 in lymphoplasmacytic lymphoma diagnosis and pathogenesis. Hematology Am Soc Hematol Educ Program 2014;2014:113-8.  Back to cited text no. 64
Menter T, Dirnhofer S, Tzankov A. LEF1: A highly specific marker for the diagnosis of chronic lymphocytic B cell leukaemia/small lymphocytic B cell lymphoma. J Clin Pathol 2015;68:473-8.  Back to cited text no. 65
Bartl R, Frisch B, Fateh-Moghadam A, Kettner G, Jaeger K, Sommerfeld W. Histologic classification and staging of multiple myeloma. A retrospective and prospective study of 674 cases. Am J Clin Pathol 1987;87:342-55.  Back to cited text no. 66
Lorsbach RB, Hsi ED, Dogan A, Fend F. Plasma cell myeloma and related neoplasms. Am J Clin Pathol 2011;136:168-82.  Back to cited text no. 67
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999;17:3835-49.  Back to cited text no. 68
Fermand JP, Brouet JC. Heavy-chain diseases. Hematol Oncol Clin North Am 1999;13:1281-94.  Back to cited text no. 69
Colomo L, Loong F, Rives S, Pittaluga S, Martínez A, López-Guillermo A, et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am J Surg Pathol 2004;28:736-47.  Back to cited text no. 70
Delecluse HJ, Anagnostopoulos I, Dallenbach F, Hummel M, Marafioti T, Schneider U, et al. Plasmablastic lymphomas of the oral cavity: A new entity associated with the human immunodeficiency virus infection. Blood 1997;89:1413-20.  Back to cited text no. 71
Dong HY, Scadden DT, de Leval L, Tang Z, Isaacson PG, Harris NL. Plasmablastic lymphoma in HIV-positive patients: An aggressive Epstein-Barr virus-associated extramedullary plasmacytic neoplasm. Am J Surg Pathol 2005;29:1633-41.  Back to cited text no. 72
Valera A, Balagué O, Colomo L, Martínez A, Delabie J, Taddesse-Heath L, et al. IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. Am J Surg Pathol 2010;34:1686-94.  Back to cited text no. 73
Vega F, Chang CC, Medeiros LJ, Udden MM, Cho-Vega JH, Lau CC, et al. Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. Mod Pathol 2005;18:806-15.  Back to cited text no. 74
Taddesse-Heath L, Meloni-Ehrig A, Scheerle J, Kelly JC, Jaffe ES. Plasmablastic lymphoma with MYC translocation: Evidence for a common pathway in the generation of plasmablastic features. Mod Pathol 2010;23:991-9.  Back to cited text no. 75
Elyamany G, Al Mussaed E, Alzahrani AM. Plasmablastic lymphoma: A review of current knowledge and future directions. Adv Hematol 2015;2015:315289.  Back to cited text no. 76
Delsol G, Lamant L, Mariamé B, Pulford K, Dastugue N, Brousset P, et al. A new subtype of large B-cell lymphoma expressing the ALK kinase and lacking the 2; 5 translocation. Blood 1997;89:1483-90.  Back to cited text no. 77
Morgan EA, Nascimento AF. Anaplastic lymphoma kinase-positive large B-cell lymphoma: An underrecognized aggressive lymphoma. Adv Hematol 2012;2012:529572.  Back to cited text no. 78
Laurent C, Do C, Gascoyne RD, Lamant L, Ysebaert L, Laurent G, et al. Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: A rare clinicopathologic entity with poor prognosis. J Clin Oncol 2009;27:4211-6.  Back to cited text no. 79
Gesk S, Gascoyne RD, Schnitzer B, Bakshi N, Janssen D, Klapper W, et al. ALK-positive diffuse large B-cell lymphoma with ALK-Clathrin fusion belongs to the spectrum of pediatric lymphomas. Leukemia 2005;19:1839-40.  Back to cited text no. 80
Said JW, Tasaka T, Takeuchi S, Asou H, de Vos S, Cesarman E, et al. Primary effusion lymphoma in women: Report of two cases of Kaposi's sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women. Blood 1996;88:3124-8.  Back to cited text no. 81
Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 1995;332:1186-91.  Back to cited text no. 82
Horenstein MG, Nador RG, Chadburn A, Hyjek EM, Inghirami G, Knowles DM, et al. Epstein-Barr virus latent gene expression in primary effusion lymphomas containing Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8. Blood 1997;90:1186-91.  Back to cited text no. 83
Cobo F, Hernández S, Hernández L, Pinyol M, Bosch F, Esteve J, et al. Expression of potentially oncogenic HHV-8 genes in an EBV-negative primary effusion lymphoma occurring in an HIV-seronegative patient. J Pathol 1999;189:288-93.  Back to cited text no. 84
Chadburn A, Hyjek E, Mathew S, Cesarman E, Said J, Knowles DM. KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma. Am J Surg Pathol 2004;28:1401-16.  Back to cited text no. 85
Brimo F, Michel RP, Khetani K, Auger M. Primary effusion lymphoma: A series of 4 cases and review of the literature with emphasis on cytomorphologic and immunocytochemical differential diagnosis. Cancer 2007;111:224-33.  Back to cited text no. 86
Beaty MW, Kumar S, Sorbara L, Miller K, Raffeld M, Jaffe ES. A biophenotypic human herpesvirus 8 - Associated primary bowel lymphoma. Am J Surg Pathol 1999;23:992-4.  Back to cited text no. 87
Møller HE, Preiss BS, Pedersen P, Kristensen IB, Hansen CT, Frederiksen M, et al. Clinicopathological features of plasmablastic multiple myeloma: A population-based cohort. APMIS 2015;123:652-8.  Back to cited text no. 88
Simonitsch-Klupp I, Hauser I, Ott G, Drach J, Ackermann J, Kaufmann J, et al. Diffuse large B-cell lymphomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome. Leukemia 2004;18:146-55.  Back to cited text no. 89
Petitjean B, Jardin F, Joly B, Martin-Garcia N, Tilly H, Picquenot JM, et al. Pyothorax-associated lymphoma: A peculiar clinicopathologic entity derived from B cells at late stage of differentiation and with occasional aberrant dual B- and T-cell phenotype. Am J Surg Pathol 2002;26:724-32.  Back to cited text no. 90
Ferry JA. Burkitt's lymphoma: Clinicopathologic features and differential diagnosis. Oncologist 2006;11:375-83.  Back to cited text no. 91
Huppmann AR, Roullet MR, Raffeld M, Jaffe ES. Angioimmunoblastic T-cell lymphoma partially obscured by an Epstein-Barr virus-negative clonal plasma cell proliferation. J Clin Oncol. 2013;31:e28-30.  Back to cited text no. 92

Correspondence Address:
Anand S Lagoo
Department of Pathology, Duke University Medical Center, PO Box 3712 DUMC, Durham, NC 27710
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.191756

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1], [Table 2]

This article has been cited by
1 Acantholytic Squamous Cell Carcinoma: a Diagnostic Pitfall on Cytology
Md Ali Osama, Kavita Gaur, Priti Chatterjee, Kiran Agarwal, Divya Jyoti
Indian Journal of Surgical Oncology. 2023;
[Pubmed] | [DOI]
2 An autopsy case of acute myocarditis with unique lymph node findings characterized by the proliferation of reactive plasmablasts
Haruo Ohtani, Yoshihiro Nozaki, Takashi Murakami, Lisheng Lin, Junko Shiono, Masaaki Miyazawa
Journal of Clinical and Experimental Hematopathology. 2020; 60(3): 108
[Pubmed] | [DOI]
3 Acute liver injury in the course of lymphoplasmacytic lymphoma
Dorota Kuzemko-Baranowska, Dariusz Baranowski, Andrzej Prystupa
Current Issues in Pharmacy and Medical Sciences. 2019; 32(1): 14
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

    Reactive Lymphad...
    Small B-Cell Lym...
    Plasma Cell Neop...
    Large B-Cell Lym...
    T-Cell Lymphoma ...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded802    
    Comments [Add]    
    Cited by others 3    

Recommend this journal