Primary Extranodal Lymphoma – A Three Year Study in a Tertiary Care Centre

Hematolymphoid Tumors of the Head and Neck

Background: Geographically there is considerable variation exists in epidemiology of extra nodal lymphomas. Aim: The aim was to study the epidemiological and histomorphological trends of Primary Extra Nodal Lymphoma (P-ENL) in India. Material &Methods: The biopsy materials from seventy patients with P-ENL (46 male, 24 female, M: F= 1.92:1), diagnosed over a period of two year (2014-2016), were analyzed and pathologically subclassified according to the 2008 World Health Organization (WHO) classification criteria. Results: Maximum incidence of P-ENL including both sexes was seen in age group 41-60 years. P-ENL constituted 23.72% and secondary extra nodal lymphomas constituted 6.7% of all lymphomas. 98.5% cases of P-ENL were Non-Hodgkin’s Lymphomas and 1.4% cases were Hodgkin’s lymphoma. The most common site involved by P-ENL was gastrointestinal tract 48.57%, followed by nasopharynx 12.8%, testis 8.4% and salivary gland 7.1%. DLBCL was the commonest lymphoma (72.8%) at all extranodal sites. B-cell phenotype predominated being 94.3% cases, followed by T-cell phenotype being 5.7% cases of P-ENL. Conclusions Gastrointestinal tract was the most common site involved by P-ENL followed by nasopharynx. Diffuse large B-cell lymphoma (DLBCL) was the most common subtype followed by marginal zone lymphoma. Majority of P-ENL cases were seen in immunocompetent hosts having a favorable prognosis.

TO THE EDITOR: Recently, primary extranodal non-Hodgkin's lymphoma (NHL) has gained considerable attention. Many controversies are associated with primary extranodal NHL, mainly due to inadequate and contradictory literatures, and lack of uniformity in definition, clinicopathological characteristics, and clinical outcomes according to the involved sites. Jang et al. put forth prospects for further research to evaluate primary extranodal DLBCL [1]. Although they concluded that rituximab had no role in the treatment of primary extranodal DLBCL, their report included several limitations that were obstacles to achieve conclusive results. The diversity in clinical presentation, morphology, immunophenotype, and genetic alterations strongly suggest that DLBCL belongs to a heterogeneous group of aggressive B-cell lymphomas. Extranodal disease is the predominant disease manifestation (incidence, about 40%) among DLBCL patients. Even in patients with stage I disease, 56% had extranodal DLBCL [2]. On the basis of the results of routine staging, the authors defined PENL (primary extranodal lymphoma) as a lymphoma with no or minor nodal involvement, along with a clinically dominant extranodal component. The definition of extranodal disease has been controversial, particularly in the presence of both nodal and extranodal manifestations. The designation of stage III and IV lymphomas as PENLs is debatable, since many clinicians consider only stage I and II presentations as primary extranodal disease [3]. For patients in the advanced stage of disease, this diagnostic approach may be inappropriate, because many extranodal lymphomas can disseminate and vice versa. In the above study, patients with stage III or IV disease constituted more than 50% of all subjects. Therefore, this definition for PENL inevitably introduces a selection bias. The second controversial issue is the different prognosis according to the involved site. Lopez-Guillermo et al. [4] reported that the clinical characteristics of nodal and extranodal DLBCLs were heterogeneous. Lymphomas arising from two specific sites [Waldeyer's ring (nodal) and gastrointestinal region (extranodal)] showed very favorable characteristics at diagnosis (e.g., early stage, absence of bone marrow involvement, normal serum LDH level, and low-risk IPI), whereas DLBCLs arising in the remaining areas (lymph nodes or other extranodal sites) presented with poorer diagnostic characteristics. In terms of response to therapy, risk of relapse and overall survival, both Waldeyer's ring and gastrointestinal lymphomas showed notably better outcomes than those shown by the other groups [4, 5]. Thus, not only the nodal or extranodal presentation, but also involvement of specific sites may be related to particular clinicobiological characteristics and disease outcomes. The authors did not provide detailed information about the involved sites and differences in patient's characteristics between the extranodal and nodal disease groups. Primary extranodal DLBCLs, according to the involved site, may be considered as different entities with different natural histories, therefore, inference from figures should be dealt with caution. Therefore, further research using population-based studies is needed to achieve conclusive results for the diagnosis of primary extranodal DLBCL. Furthermore, the study of unresolved issues, including ambiguous definition, different clinicobiological characteristics, and gene profiles of primary extranodal DLBCL arising from different sites is warranted.

Primary extranodal and nodal non-Hodgkin's lymphoma: A survey of a population-based registry

Primary extranodal lymphoma (pENL) refers to group of disorders arising from tissues other than lymph nodes and even from sites, which normally do not contain lymphoid tissue. This study was undertaken to ascertain the prevalence, anatomical distribution, and histological subtypes of extranodal non-Hodgkin lymphoma (NHL) from a tertiary care institute in Southern India. This was a cross-sectional study conducted in the Department of Pathology over a period of 3-years. Detailed clinical history, routine complete blood count, microbiological status was obtained from the medical records. Hamatoxylin and eosin slides were reviewed and immunohistochemistry was performed using a panel of antibodies depending on the morphology. All cases were classified based upon morphologic and immunophenotypic criteria according to World Health Organization 2008 classification. Primary extranodal NHL constituting 22.6% (68/300) of all NHL and the majority of patients were from higher age group with peak incidence seen in fourth to fifth decade of life. In the pediatric population, the most common site is ileo-caecal region (42.8%) and the most common morphology is lymphoblastic lymphoma (42.8%). Similarly in the adult population head and neck was the most common site constituting 36% and diffuse large B-cell lymphoma is the most common morphological subtype comprising 54% of all extranodal lymphomas. Although the reported incidence of pENL is low in India compared to other parts of the world, the possibility of pENL should always be kept in mind even though it arises in an extranodal site.

We sought to determine the frequency of primary extranodal lymphoma (ENL) and its characteristics in Kanagawa, a human T-cell leukemia virus type 1 (HTLV-1) nonendemic area in Japan. Subjects were 847 newly diagnosed patients with malignant lymphoma at the Yokohama City University Hospital and 8 affiliated hospitals mainly located in Kanagawa prefecture from 1999 to 2005. We compared the clinicopathological characteristics of primary ENL with primary nodal lymphoma (NL). Histological specimens were evaluated according to the World Health Organization classifications. A total of 395 (46.6%) and 452 (53.4%) patients had primary ENL and primary NL, respectively. The frequency of primary ENL increased with age. Primary extranodal sites included the gastrointestinal tract (30.4%), Waldeyer's ring (17.8%), orbits (7.0%), soft tissue and subcutaneous tissue (5.2%), bone (4.6%), skin (4.3%), thyroid gland (4.3%), testis and prostate (3.3%), bone marrow (3.3%), nasal and paranasal cavities (2.6%), salivary glands (2.3%), lung and pleura (2.0%), breast (1.8%), central nervous system (1.0%), uterus and ovary (0.5%), and others (9.8%). Among the 395 cases of primary ENL, diffuse large B-cell lymphoma (61.2%) was most frequently diagnosed, followed by extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (13.3%) and follicular lymphoma (5.6%). The frequency of primary ENL is approximately 50% of the total lymphoma cases in Kanagawa, an HTLV-1 nonendemic area in Japan. This frequency appears to be higher than that in Western countries.

A 25-year-old woman presented with a fever of 1-month duration. There were no specific localizing signs or symptoms. Apart from a raised serum C-reactive protein (108 mg/L, normal 0.2–8.8 mg/L) and erythrocyte sedimentation rate (129 mm/h, normal 3–15 mm/h), the blood tests were unremarkable, including a normal full blood count, autoimmune screen, and microbiology tests. The patient completed a course of antibiotics, but the fever persisted. A contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis was performed to evaluate the cause of the prolonged fever. The CT scan showed multiple hypodense lesions in both kidneys (Fig. 1, white arrows), bulkiness of both ovaries (Fig. 1, black arrows), and permeative osteolytic lesions in the bony pelvis (Fig. 1, arrowhead). The differential diagnoses of a malignancy and an infection were entertained. AnF-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan was performed to evaluate the cause of fever, assess the extent of involvement, and determine the most suitable site of biopsy. The FDG PET/CT scan showed multiple hypermetabolic lesions in both kidneys (maximum standardized uptake value, SUVmax 16; Fig. 2, arrows), both ovaries (SUVmax 24; Fig. 2, dotted arrow), and multiple bones of the axial and appendicular skeleton, including the calvarium, clavicles, scapulae, multiple ribs bilaterally, multiple vertebrae, bony pelvis, and proximal femora (SUVmax 27; Fig. 2, arrowheads). No nodal disease was detected. A bone marrow aspiration and trephine biopsy were performed, and the results revealed the diagnosis of a diffuse large B-cell lymphoma (DLBCL). The imaging and histopathological findings were compatible with a primary multifocal extranodal DLBCL with extensive involvement of the kidneys, ovaries, and bones. After three cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), a repeat FDG PET/CT scan showed a complete metabolic resolution of the lesions in the kidneys, ovaries, and bones, indicative of an excellent treatment response (Fig. 3). The patient went on to complete six cycles of chemotherapy, and achieved complete remission. DLBCL is the largest subtype of non-Hodgkin lymphoma (NHL). Extranodal involvement in the NHL is common with primary extranodal lymphoma accounting for approximately one third of the NHL cases [1, 2]. Extranodal lymphoma can occur in any organ, and can be multifocal involving two or more organs. The most common site of primary extranodal lymphoma is the gastrointestinal tract; the other common sites include the skin, central nervous system and testis [2–4]. Kidneys and ovaries are relatively uncommon sites of primary extranodal lymphoma [2–4]. Concurrent involvement of the kidneys, ovaries and bones in a primary multifocal extranodal lymphoma is an uncommon presentation of a common condition. Lymphoma is a known cause of a fever of unknown origin (FUO). FDG PET/CT scan has been shown to be useful in the evaluation of FUO [5]. FDG PET/CT scan allows a quick and non-invasive screen of the whole body, and is useful in localizing the source of fever and determining the most accessible site to guide further diagnostic procedures like a biopsy [5]. Hence performing an FDG PET/CT early in the investigation of a prolonged fever may potentially lead to a quicker diagnosis and help to expedite the treatment. S.-J. Lu (&) M. M. L. Tan S. Osmany Department of Nuclear Medicine and PET, Singapore General Hospital, Outram Road, Singapore 169608, Singapore e-mail: suat_jin_lu@yahoo.com

ABSTRACTThe primary lacrimal sac involvement by malignant tumors is uncommon. The most commonly seen malignant tumors of the lacrimal sac are those of epithelial origin. Primary extranodal non-Hodgkin's lymphoma (PE-NHL) of the lacrimal sac is rare. We hereby present a rare case of primary non-Hodgkin's lymphoma (NHL) of the lacrimal sac with extension to the ipsilateral nasal cavity through the nasolacrimal duct.How to cite this articleMittal HK. A Unique Case of Primary Extranodal Non-Hodgkin's Lymphoma of the Lacrimal Sac with Extension to Ipsilateral Nasal Cavity. Int J Otorhinolaryngol Clin 2014;6(3):103-105.

The aim of this study was to assess the epidemiological and clinicopathological characteristics of primary extranodal non-Hodgkin's lymphoma (pENL) patients, focusing on treatment and survival outcome. Between October 2003 and March 2012, 802 patients with non-Hodgkin's lymphoma (NHL) were diagnosed and treated in two different cancer centers of Southern Turkey. pENL, constituted 12.4% (100/802) of all NHL studied during this period. Median age of the patients was 56 years (range 17-87 years) and the male: female distribution was 3:2. Eighty-five of 100 patients (85%) were in stage I/II, 9/100 (9%) in stage III, whereas 6/100 (6%) were in stage IV. Head and neck constituted the most common site (51/100, 51%), followed by gastrointestinal tract (GIL) (37/100, 37%), and cerebrum (CL) (5/100, 5%). Diffuse large B cell lymphoma (DLBCL) was the most common histological type, observed in 53% of patients, followed by marginal zone extranodal lymphoma (13%). Most of patients (76%) received a CHOP containing regimen. Complete remission (CR) were achieved in 71% of patients. The median follow-up duration of all patients was reported as 37.6 months (range, 0.8-165 months). This period was reported as 137.5 months (range, 117.5- 1578.6 months) in gastrointestinal lymphoma (GIL) patients, 119.0 months (range, 91.8-146.1 months) in head and neck lymphoma (HNL) patients, and 18.4 months (range, 12.6-24.1 months) in cerebral lymphoma (CL) patients. Head and neck, and the gastrointestinal tract were the two most common extranodal sites observed. Histologically DLBC accounted for the majority of cases. Most patients were on earlier stages, had low-low intermediate IPI scores and had a favorable prognosis.

Around 30% of all non-Hodgkin lymphoma (NHL) cases arise from extranodal sites. Often the primary extranodal presentation requires site-specific strategies either for diagnosis or therapy. However, several issues remain controversial such as the definition itself of primary extranodal lymphoma, and the most appropriate staging system to characterize the disease extent. Moreover, the specific presenting sites may have per se prognostic implications. The vast majority of the published reports on primary extranodal lymphomas are represented by single-institution retrospective studies. In most clinical trials the primary extranodal lymphomas are often included together with the nodal ones and only a few studies have investigated the peculiarity of extranodal lymphomas. This review summarizes the recent advances in B-cell extranodal lymphomas, addressing the critical points in the management of the more frequently involved sites.

Primary extranodal diffuse large b-cell lymphoma of the calf muscle mimicking a carcinoma: A rare case report

Twenty-seven cases of primary extranodal oral B-cell lymphoma and 22 cases of primary maxillofacial nodal B-cell lymphoma were investigated for the presence of apoptotic cells and the expression of apoptosis-related gene products by terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) and immunohistochemistry. The majority of extranodal oral diffuse large B-cell lymphomas (17/25, 68%) and maxillofacial nodal diffuse large B-cell lymphomas (14/16, 88%) contained no or less than 10% apoptotic cells. Whereas the majority of extranodal oral diffuse large B-cell lymphomas (18/25, 72%) and maxillofacial nodal diffuse large B-cell lymphomas (13/16, 81%) contained more than 10% of Ki-67-positive cells. Bcl-2-, Bax-, p53- and Ki-67-positive rates were higher in maxillofacial nodal diffuse large B-cell lymphomas than in extranodal oral diffuse large B-cell lymphomas, but only Bax (chi2 test, 0.01<P<0.025) and p53 (chi2 test, 0.005<P<0.01) had significant differences. Extranodal oral diffuse large B-cell lymphomas had a higher frequency of TUNEL expression than maxillofacial nodal diffuse large B-cell lymphomas. In maxillofacial nodal diffuse large B-cell lymphomas, stage III and stage IV tumors had a significantly higher frequency of Bcl-2 expression than stage I and stage II tumors (Fisher's exact test, P<0.01). These findings indicated that in the majority of both extranodal oral and maxillofacial nodal diffuse large B-cell lymphomas, apoptosis was inhibited - whereas proliferative activity was accelerated. Impairment of apoptosis and apoptotic related gene products may have a more important relation to maxillofacial nodal diffuse large B-cell lymphoma than extranodal oral diffuse large B-cell lymphoma.

Primary mediastinal non-Hodgkin lymphomas (PM-NHLs) represent ∼5% of all non-Hodgkin lymphomas (NHLs) and comprise lymphomas of B-cell and T-cell origin. PM-NHLs are defined as involvement of mediastinal lymph nodes, thymus, and/or mediastinal organs (heart, lung, pleura, pericardium) by NHL without evidence of systemic disease at presentation. The clinical scenario is variable and depends on the lymphoma subtype. The radiologic presentation is also variable ranging from a mediastinal mass with or without superior vena cava syndrome, a pleural or a cardiac mass associated with effusion, or as an effusion only. The diagnosis of PM-NHLs can only be established by microscopic evaluation, and therefore, general pathologists should be aware of these tumors and familiar with their diagnostic approach. The most common anterior mediastinal NHLs (90% to 95%) are primary mediastinal (PM) large B-cell lymphoma and T-lymphoblastic lymphoma. Thymic marginal zone lymphoma and mediastinal gray zone lymphoma are very rare. The remainder PM-NHLs involving middle or posterior mediastinum include diffuse large B-cell lymphoma (DLBCL) and rare cases of T-cell lymphoma, including anaplastic large cell lymphoma and breast implant-associated anaplastic large cell lymphoma extending to the anterior mediastinum. Primary pleural and cardiac NHLs are mostly DLBCLs. Other rare subtypes of PM-NHLs include DLBCL associated with chronic inflammation/pyothorax-associated lymphoma, fibrin-associated DLBCL (both Epstein-Barr virus positive), and pleural and/or pericardial primary effusion lymphoma (human herpesvirus-8 positive/Epstein-Barr virus positive). We review the historical aspects, epidemiology, clinicoradiologic features, histopathology, immunohistochemistry, differential diagnosis, and relevant cytogenetic and molecular features of the remaining mediastinal B-cell lymphomas, including primary thymic marginal zone lymphoma of the mucosa-associated lymphoid tissue type, other PM small B-cell lymphomas, PM plasmacytoma, and the most relevant PM T-cell lymphomas.

Background: Primary extranodal non-Hodgkin's lymphoma is emerging as a common entity that presents with diverse clinical features, morphology and immunophenotyping patterns.&#x0D; Aim: The aim of this study is to analyze the clinicopathological and immunohistochemical features in patients with primary extranodal non-Hodgkin's lymphoma.&#x0D; Settings and Design: This is a retrospective observational study from pre-recorded hospital data.&#x0D; Materials and Methods: The data of all histologically confirmed patients with non-Hodgkin's lymphoma were retrieved to identify those confirmed as primary extranodal non-Hodgkin's lymphoma among patients attending King Abdulaziz University Hospital, Jeddah, Saudi Arabia over the last 12 years (January 2003 - May 2015). Retrieved data was analyzed with regards to the demography, clinical features, histopathological and immunohistochemical features. Lymphoma of the study group were classified according to World Health Organization classification of lymphomas 2008.&#x0D; Result: A total of 218 patients with histologically confirmed non-Hodgkin's lymphoma were identified. Seventy-nine (36.2%) had primary extranodal non-Hodgkin's lymphoma. The most common age group affected was 20-39 years for both genders. Gastrointestinal system was the most frequently involved system for both genders. Colon was the most common site involved among males, while thyroid and thymus were the most common sites involved among females. Diffuse large B cell lymphoma was the most common histological type.&#x0D; Conclusion: Primary extranodal non-Hodgkin's lymphoma is common in Saudi Arabia affecting males and females almost equally in the third and fourth decades of life, with diffuse large B cell lymphoma being the most common histologic subtype.

Extranodal lymphoma: a reappraisal