Introduction
First definition of Extra Nodal Non Hodgkin Lymphomas (EN NHL) were first given by Dawson for gastrointestinal lymphomas.1 The original Dawson criteria defined primary gastric lymphoma. It was later refined by Lewin2 and Herrmann,3 these criteria were relaxed to allow for contiguous involvement of other organs (e.g. liver, spleen), and for distant nodal disease, providing that the extranodal lesion was the presenting site and, after routine staging procedures, constituted the predominant disease bulk, to which primary treatment must be directed.4
The definition of primary EN-NHL is a controversialissue, especially in patients where both nodal andextranodal sites are involved. Some series on primary ENNHLhave included patients with only localized disease. On the other hand, studies that use more liberal criteriafor EN-NHL include patients with disseminated disease(Rudders et al. Moller et al., 2004).5, 6
Clearly, any chosen definitioninevitably introduces a selection bias; a Dutch study from a different geographical population-based registry showedthat the frequency of extranodal NHL fluctuatedfrom 20% to 34%, depending on theadopted designation criteria.7
Various studies havereported incidence rates ranging from 10 to 48%.8, 9 The incidence of extranodal NHL in developing countries is largely unknown.
In the population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, approximately 30% of all lymphomas were extranodal and almost half of all extranodal NHL cases reported had diffuse large B-cell lymphoma (DLBCL) histology.10
With this case series we aim to describe the anatomic distribution, clinical features, Immunohistochemical typing and outcome of EN NHL patients.
Materials and Methods
This is a descriptive case series of 17 cases of primary ENNHLs, collected during a period of 1 year. The number includes all cases of ENNHL diagnosed and confirmed on routine histopathology in the department of pathology. The tissue processing was done in 10% formalin and 5 paraffin sections were stained with hematoxylin and eosin (HE). Immunohistochemistry (IHC) was performed using a panel of antibodies depending on the morphology. The IHC was performed manually on the paraffin embedded tissue sections by using a panel of monoclonal antibodies. Antigen retrieval was done by pretreatment of paraffin sections by heating in a microwave in 0.01 M citrate buffer (pH6.0). The panel of antibodies used for IHC includes pancytokeratin, leukocyte common antigen, CD3, CD5, CD19, CD20, CD23, CD10, Bcl2, Bcl6, Tdt. Data pertaining to patients’ demography, clinical presentation, immune status, routine complete blood count, and microbiological (HIV, EBV, H.pylori, HCV, and HBV) status were obtained from the LIS. Molecular diagnostic techniques such as cytogenetics/fluorescence in situ hybridization were not performed in any of the cases
The cases includes all patients who present with NHL that apparently originated at an extranodal site, even in the presence of disseminated disease, as long as the extranodal component was clinically dominant as proposed by Krol et al.11 Cases of tonsilar and Waldeyer’s ring lymphoma were excluded due to controversial status as extranodal site.12
All cases were classified based upon morphologic and immunophenotypic criteria according to World Health Organization (WHO) 2008 classification.13 Clinical stage was defined according to the Ann Arbor classification.14
Results
Primary extranodal NHL constituted 26.9% (17/63) of all NHL diagnosed over a period of 1-year were included in the study. Majority of our patients were from higher age group, presenting in sixth decade, though the age range was wide between 5-92 years. Our study included 12 males and 5 females, with a male: female ratio of 2.4:1. Figure 1 describes the distribution of cases according to the site. Figure 2 describes the typing of lymphomas according to Immunohistochemistry. Figure 3 describes the clinical presentation of all cases.
Ann Arbor Staging was done in 16/17 cases where 35% (6/17) belonged to stage I, 35% (6/17) cases belonged to stage II, 17.6 (3/17) belonged to stage III and 1.5% (1/17) belonged to stageIV as described in Table 1. Eastern cooperative oncology group performance scale (ECOG) was also calculated in these cases which are described in Table 2.
Table 1
Stage (Ann Arbor system)
|
Ann Arbor Stage |
Number of patients |
|
I |
6 (35%) |
|
II |
6 (35%) |
|
III |
3 (17.6%) |
|
IV |
1 (5.8%) |
Table 2
ECOG=Eastern cooperative oncology group performance scale
|
ECOG Score |
Number of patients |
|
0 |
3 |
|
1 |
4 |
|
2 |
4 |
|
3 |
3 |
|
4 |
2 |
Figure 1
H&E showing replacement of normal lung parenchyma with lymphoid cells, 2) CD79a Positive in lymphoid cells, 3) CD3 Positive.
Figure 2
H&E showing lymphocytic infiltration in a cases of retroperitoneal mass, 2) Image shows IHCTdT positivity in a case of burkitt lymphoma
Discussion
Primary extra nodal lymphomas have long been known for their heterogeneity because of its varied epidemiology and etiology. Studies from Western countries have reported the occurrence of extranodal NHL as 24-48% of all NHL.14, 15, 16, 11 In contrast to Asian studies the incidence varies from widely in China (44.9-61.4%), however most of country claim similar incidence of around 40 to 50%.17, 18, 19, 20 In India, the incidence and the sites varies widely. A study from Northern India by Singh et al. showed extranodal lymphomas constitute 44% with the most common site being the head and neck.21 whereas a study conducted by Padhi et al. from Southern India showed extranodal lymphomas constituted 22% and the most common site being the central nervous system.23Western India shows incidence of 28% and GIT being the most common site that is affected.22 Our study showed incidence of 25.3% with Nasopharynx (4/17) being the most common site of EN NHL, followed by retroperitoneal masses (3/17). The incidence is much lower, which may be due to shorter duration of the study and due to variation in genetic and ethnic factors, as well as the diverse definition criteria. Diffuse large B-cell lymphoma (8/17) was the most common histological subtype found in the current series. It is in concordance with many studies on EN-NHL.21, 23, 24, 25, 26 Nasopharyngeal lymphoma is a rare extranodal lymphoma with a variety of histopathologic subtypes, and the incidences of different subtypes are quite different among different areas . Diffuse large B cell lymphoma (DLBCL) and NK/T cell lymphoma (NKTCL) are the two most common pathologic diagnoses.27, 28 The prognosis is different in different forms, however a correlation with disease stage has been noted. The current series report 2 cases of NP DLBCL, while other 2 were T cell lymphoma. Ye et al. also found an equal incidence of B-cell (51%) and T-cell (49%) lymphomas in the nasopharynx among 54 cases.29 While, in the another study of 113 patients reported by Cheung et al. lymphoma involving the nasal cavity was mostly of NK/T-cell or T-cell lineage, while almost half of the lymphomas involving the nasopharynx were of B-cell lineage.30 one case of DLBCL of Central Nervous System, another nasopharyngeal T cell lymphoma was seen in HIV positive patients. Extranodal DLBCL is the most commonly presenting lymphomas in immunocompetent HIV patients, and similar to this patient presents at a higher stage of disease. However Tcell lymphoma is a very rare such patients. The present case series includes one case of Primary Pulmonary Lymphoma (PPL), which histologically was B-cell NHL. PPL is a very rare neoplasms, presenting as only 0.4% of lymphomas. 31 It is defined as a clonal lymphoid proliferation affecting one or both lungs in a patients with no detectable extrapulmonary involvement at diagnosis or subsequent 3 months.32 One large series of 70 patients reported 94% survival at 5 years for low grade PPL.32, 33, 34
Conclusion
Primary extranodal lymphomas constitute a diverse group of hematolymphoid malignancies whose prognosis depends upon the primary site. The incidence of pENL is low in India compared to data from other parts of the world. With this case series we add to the literature basic knowledge about ENNHL.
