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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 10  |  Issue : 2  |  Page : 114-118

Histopathologic spectrum of lymph node disease in a lagos facility


1 Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria
2 Department of Cellular Pathology, Betsi Cadwaladr University Health Board, Bodelwyddan, Wales, UK
3 Department of Cellular Pathology, Queen's Hospital, Romford, Essex, UK

Date of Submission24-Feb-2019
Date of Decision21-Mar-2019
Date of Acceptance26-Apr-2019
Date of Web Publication6-Dec-2019

Correspondence Address:
Dr. Olubanji Ajibola Oguntunde
Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, PMB 12003, Lagos
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/atp.atp_8_19

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  Abstract 

Background and Objective: Hematopathology is often a technical and challenging aspect of pathology, requiring robust ancillary testing and second specialist opinion, both of which are not readily available and affordable to the Nigerian population. The aim of this study, therefore, was to determine the histological spectrum of lymph node diseases and highlight the diagnostic challenges. Methodology: A retrospective review of lymph node biopsies submitted to The Specialist Laboratories, Lagos, Nigeria, over an 8-year period was carried out. A proportion of these had a specialist's second opinion and ancillary immunohistochemistry testing where necessary. Results: Two hundred and ten lymph node biopsies were studied. Majority of the cases were diagnosed as nonspecific reactive changes (31.0%). This was followed by metastases to the lymph nodes (22.9%) and lymphomas (18.6%). Non-Hodgkin's lymphoma accounted for 79.5% of lymphomas, of which small cell lymphoma (35.5%) and diffuse large B-cell lymphoma (29.0%) were the most predominant subtypes. There was a 62.1% concordance between the preliminary and final diagnoses. Conclusion: These morphologic findings are in keeping with those in published literature. A significant number of discordant cases highlight the need for specialist training in hematopathology as well as the establishment of well-equipped facilities for accurate and cost-effective diagnosis.

Keywords: Hematopathology, histopathologic, lymph node, lymphoma, spectrum


How to cite this article:
Oguntunde OA, Ikeri NZ, Igbokwe U, Abdulkareem FB, Banjo AF. Histopathologic spectrum of lymph node disease in a lagos facility. Ann Trop Pathol 2019;10:114-8

How to cite this URL:
Oguntunde OA, Ikeri NZ, Igbokwe U, Abdulkareem FB, Banjo AF. Histopathologic spectrum of lymph node disease in a lagos facility. Ann Trop Pathol [serial online] 2019 [cited 2020 Nov 26];10:114-8. Available from: https://www.atpjournal.org/text.asp?2019/10/2/114/272431


  Introduction Top


Lymph nodes are involved by a very wide range of pathologic conditions and are, therefore, commonly biopsied for histologic analysis. When lymphoma features in the differential diagnoses, analyses are often very technical requiring second opinion by a specialist haematopathologist.[1] It is not surprising therefore that there is paucity of data on the specific lymphoma subtypes in our environment where ancillary testing and specialist's opinion are not readily available or affordable. Indeed, only a few Nigerian studies with the required corroboratory ancillary testing were found after an extensive search.[2],[3],[4],[5],[6] There has also been a change in the epidemiology of lymph node diseases over the years. Burkitt lymphoma, once the most common childhood malignancy in Lagos and other parts of Southwest Nigeria, now occurs less commonly than retinoblastoma.[7],[8],[9] This has been attributed to the better control of malaria, a cofactor for its occurrence. A reduced incidence has also been reported in other parts of Southwest Nigeria. It, however, remains the most common childhood malignancy in the northern regions of the country.[10],[11] In adults, lymphomas remain a leading cause of cancer mortality, especially with the advent of HIV – AIDS, making studies on it important in our environment.[12]

The aim of this study was, therefore, to give an update of the morphologic spectrum of the various lymph node diseases seen in our facility as well as to highlight the challenges faced with lymphoma diagnosis.


  Methodology Top


This study was carried out to review and categorize all lymph node specimens received at The Specialist Laboratories, Lagos, Nigeria, from January 2010 to August 2017. Only cases where the lymph nodes were being investigated as the primary clinical problem were studied. Lymph nodes received as part of resection specimen, for example, mastectomy and colectomy were, therefore, excluded from the study. Second-opinion cases from our institution are routinely sent to a referral center in the United Kingdom for second opinion and ancillary testing when a diagnosis of lymphoma is entertained. The antibody panels used for ancillary immunohistochemistry include CD3, CD5, CD10, CD15, CD20, CD23, CD30, CD34, CD38, CD45, CD56, CD79a, cyclin D1, Bcl2, Bcl6, Ki-67, TDT, EMA, S100, ALK1, MUM1, Pax 5, and Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1). Immunohistochemical analysis for the cases was performed on 4-μformalin-fixed paraffin-embedded sections, which were stained using an automated immunostaining system with monoclonal antibodies manufactured by DAKO against each of this protein. Every other process was carried out according to the manufacturer's instruction. The data extracted from the pathology reports included the patient's age, sex, anatomical site, preliminary diagnoses, final diagnoses and the immunohistochemistry profile where present. These data were analyzed using SPSS 23 (Statistical Package for Social Sciences for Windows 22.0 IBM, Armonk, NY, USA), and the results are represented in figures and tables.


  Results Top


Two hundred and ten lymph node biopsies met the inclusion criteria for the study. Of these, 104 were female patients and 93 from males, giving a male-to-female ratio of 1:1.1. Gender was not indicated in 13 patients. The age was not specified in 21 of the patients. The peak age of involvement was 40 years, the median age was 44 years, and the age range was 2–87 years. [Figure 1] shows the age distribution of patients. The anatomical site was specified in 141 cases. The cervical and axillary lymph nodes were the most common lymph node specimens submitted for histopathologic assessment [Figure 2].
Figure 1: Age distribution of cases with lymph node disease

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Figure 2: Distribution of lymph nodes sampled by location

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The majority of lymph nodes had nonspecific reactive changes. These were followed by metastases and lymphoma [Table 1]. Of the 48 metastatic cases, 36 (75.0%) were adenocarcinomas, 5 (10.4%) were squamous cell carcinomas, 1 (2.1%) was a neuroendocrine carcinoma, and 6 (12.5%) were poorly differentiated carcinomas.
Table 1: Histologic diagnosis of lymph node disease

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Thirty-five cases (16.7%) were tuberculous lymphadenitis. A definitive diagnosis was made in these cases with either a positive Ziehl–Neelsen (ZN) stain or clinical response to therapy when histologically ZN is negative. The mean age of occurrence of tuberculous lymphadenitis was 35.2 years with a male-to female-ratio of 1:1.3, and the vast majority of these cases (81%) were found in the cervical lymph nodes. Diagnoses in the miscellaneous categories included 2 (20%) cases of Castleman disease, a case each of Rosai–Dorfman disease (10%) and Kikuchi necrotizing lymphadenitis (10%), and 6 (60%) cases of dermatopathic lymphadenopathy.

Sixty-six cases were sent for second opinion and immunohistochemistry. In 41 (62.1%) of these cases, the final diagnosis was concordant with the preliminary histologic diagnosis. Sixteen (24.2%) cases had discordance between preliminary and final diagnoses [Table 2]. In the remaining 9 cases, no preliminary diagnosis was given.
Table 2: List of discordant cases

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Thirty-nine (59%) of the 66 cases sent for immunohistochemistry and second opinion were found to be lymphomas. Of the lymphoma cases, non-Hodgkin's lymphoma (NHL) accounted for 31 (79.5%), whereas the remaining 8 (20.5%) were Hodgkin lymphoma. Small lymphocytic lymphoma (SLL) and diffuse large B-cell lymphoma (DLBCL) were the most common NHLs, whereas nodular sclerosing type was the most common Hodgkin's lymphoma subtype [Table 1]. Details of immunohistochemical profile for SLL, DLBCL, follicular lymphoma (FL), and lymphoplasmacytic lymphoma are given in [Table 3] and [Figure 3]. Only 2 (25%) of the Hodgkin's lymphoma showed positive staining for EBV LMP1. One of the two cases of anaplastic large-cell lymphoma (ALCL) was ALK-positive.
Table 3: Immunoprofile of the low-grade small cell lymphomas

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Figure 3: Photomicrograph of diffuse large B-cell lymphoma and small cell lymphoma (SLL) with their immunohistochemistry panel at × 100 a. H and E (DLBCL) b. CD20 (DLBCL) c. MUM1 (DLBCL) d. KI-67 (DLBCL) e. H and E (SLL) f. CD5 (SLL) g. CD23 (SLL) h. CYCLIN D1 (SLL)

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  Discussion Top


The most common lymph node diagnosis seen in this study was nonspecific reactive changes. This is consistent with local and international reports. This is not surprising as a wide variety of conditions such as infection, drugs, chemicals, environmental pollutants, and even malignancy are associated with this histologic pattern.[13],[14] These nonspecific changes could be in the follicular, paracortical, or sinusoidal compartments, or could have a mixed morphologic appearance.[15] Recognizing these patterns can sometimes suggest the underlying diagnosis. Reactive follicular hyperplasia is associated with rheumatoid arthritis, Sjögren syndrome, HIV-associated lymphadenopathy, or progressive transformation of lymphoid follicles.[15] Reactive paracortical hyperplasia is more often seen in the context of viral infections, immunization, or drug use. Reactive sinus hyperplasia is in relation with monocytoid B-cell hyperplasia, hemophagocytic syndromes, Whipple's disease, or lymph nodes draining sites of prostheses or malignancy.[15] Identifying the primary cause is, however, only possible in a minority of cases. As a group, reactive nonspecific lymphadenopathy is self-limiting and requires no further treatment.[15]

Tuberculous lymphadenitis, while accounting for a considerable proportion of cases, was seen in much lower frequencies compared to studies from other parts of Nigeria. In our study, they accounted for 16.7% of cases compared to 35% in Benin, 30% in Kano, and 38% in Ilorin.[16],[17],[18],[19],[20] This finding is consistent with other reports from Lagos, which have consistently shown a lower proportion of tuberculous lymphadenitis in lymph node specimen submitted to the study center.[13],[19] A closer look at these institutional studies shows a detection rate of tuberculous lymphadenitis to be 8–9/year/institution in Lagos, 5/year/institution in Benin, 12/year/institution in Ilorin, and 15/year/institution in Kano. A detection rate in Kano being almost twice that in Lagos and thrice that in Benin suggests a higher incidence of tuberculous lymphadenitis in Northern Nigeria.[16],[17],[18],[19],[20] In Bradford UK, 15% of lymph node biopsies were tuberculous, amounting to a detection rate of 17/year.[14] This is most probably due to improved access to health-care facilities in the region. Tuberculosis, therefore, occurs less commonly in Lagos and other southern parts of the country. What is consistent in all geographic locations, however, is the cervical lymph node being the most common site of tuberculous lymphadenitis as was the case in this study.[14],[15],[16],[17],[18],[19]

In this study, metastases from occult malignancies to the lymph nodes also occurred more commonly than tuberculous lymphadenitis, which is consistent with the previous reports from institutions in Lagos but at variance with those from other parts of the country.[13],[14],[15],[16],[17],[18],[19] Lagos appears to have a much higher rate of occult metastases to lymph nodes approaching a detection rate of 22 cases/year/institution. Reports from institutions in other parts of the country show a detection rate of 6/year in Benin, 8/year in Ilorin, and 9/year in Kano.[16],[17],[18],[19] It could be that the reason for this is related to the higher levels of environmental pollutants from automobiles and factories, as well as the adoption of harmful lifestyles such as cigarette smoking, high-calorie diet, late age of first confinement, and poor breastfeeding history, all of which are risk factors for the development of cancer. This will need to be further explored by more studies. Specific nontuberculous lymphadenitis is the least common type of lesion seen in most studies worldwide.[13],[14],[15],[16],[17],[18],[19] It usually requires a higher index of suspicion and often a second opinion by a specialist in hematopathology. Due to a paucity of such specialists in Nigeria, these diagnoses are rarely ever made and often limited to a diagnosis of sarcoidosis or cat-scratch disease.[16]

Due to availability of specialist's second opinion in this study, diagnoses of dermatopathic lymphadenopathy, Castleman disease, Kikuchi necrotizing lymphadenitis, and Rosai–Dorfman disease were made. This shows that rare and exotic lymph node lesions also occur in the Nigerian population. There is, therefore, a need for specialist in hematopathology and more robust ancillary testing in this country as such diagnosis can often be confused with lymphoma.

Lymphomas were seen in 18.6% of all lymph node samples received. There was slight female predominance in this study for both Hodgkin's lymphoma and NHL. Consistent with findings in the literature, Burkitt lymphoma and acute lymphoblastic lymphoma had the youngest mean age of occurrence (6 and 12 years, respectively).[13] Nodular sclerosis variant of Hodgkin's lymphoma and ALCL also had mean ages of occurrence slightly lower than other lymphoma types.[13] The cervical lymph node was the most common involved site in both the Hodgkin's lymphoma and NHL subtypes.[14] Comparison with other local studies is difficult as there are very few studies with confirmatory ancillary testing. As is the case worldwide, NHL is by far the most common histologic subtype.[21] In our study, they accounted for 79.5% of lymphomas. Comparatively, they account for 84.5% in the study by Akinde et al. in Lagos, 80% in a study from Zaria, 79.5% in Ile-Ife, 91.9% in a study from the US, and 85.6% in the UK.[2],[3],[4],[5],[20],[21] The incidence of lymphoma as a whole has been shown to be almost equal in all races, with a slightly lower rate in blacks. There is a greater variability, however, with regard to the specific lymphoma subtypes. Hodgkin's lymphoma has an almost equal incidence in blacks and whites. FL, and to a lesser extent, DLBCL and small lymphocytic lymphoma occur more frequently in whites, whereas plasma cell neoplasms, and to a lesser extent, T-cell lymphomas are seen more commonly in blacks.[20] With respect to geographical location, Burkitt lymphoma occurs far more commonly in Africa than in western populations.[22]

DLBCL and small lymphocytic lymphoma (SLL) are the most common lymphomas in most literature with DLBCL occurring more frequently than SLL.[20],[21] This was also the finding reported by Akinde et al. and Onwubuya et al. in Lagos and Ile-Ife, respectively.[2],[3],[5] In our study, the two tumors were the most common NHL subtypes, with SLL occurring slightly more frequently than DLBCL. This may likely be due to the smaller sample size of our study. It, therefore, appears that the frequency of the various subcategories of NHL follows the trends in the literature. In Zaria, however, Iliyasu et al. reported Burkitt lymphoma to be the most predominant NHL, which might suggest poorer malaria control in Northern Nigeria.[4] Peripheral T-cell lymphoma not otherwise specified (PTCL NOS) is the most common T-cell lymphoma reported in the literature.[20],[21] This was also reported by Akinde et al. in their study.[2] Our study and an Ile-ife study however reported anaplastic large cell lymphoma as the commonest T-cell lymphoma. There was no record of PTCL in both studies.

As is reported worldwide, a nodular sclerosing variant of Hodgkin's lymphoma is the most prevalent subtype of Hodgkin's lymphoma.[20],[21],[22] In our study, it accounted for 75.0% of cases. Akinde et al. and Adelusola et al. reported mixed cellularity subtype to be the more common variant in their respective studies.[2],[6] Only 25.0% of Hodgkin's lymphoma were associated with EBV LMP 1 in this study, whereas 60% was reported in Ile-Ife by Adelusola et al. It has been reported that EBV-positive Hodgkin's lymphoma is more common in developing countries where it accounts for up to 100% of cases as was reported in Kenya.[23],[24] The gold standard of EBV detection is in situ hybridization, and this will need to be performed to determine the true incidence of EBV in Hodgkin's lymphoma cases in our environment.

Lymphoma diagnosis evidently is very challenging, especially in low-to-medium income countries where the required ancillary tests and specialist in hematopathology are often in short supply. This is evidenced by a discordant rate of 24.2% in preliminary and final diagnoses shown in this study. In the majority of discrepant cases, reactive expansion of the interfollicular compartment was confused with NHL. Detailed attention to the lymph node architecture often helps to make the right diagnosis as reactive lymph nodes show the preserved architecture, do not form any discrete expansile mass, do not erode the mantles of the scattered follicles, and exhibit a mixture of lymphoid cell types which lack cellular atypia. Another lesson learnt from these discrepancies is that florid immunoblastic proliferation can be seen in viral lymphadenitis, and this must be interpreted in the context of the features of reactive changes listed above to avert misdiagnosis as lymphoma. Immunohistochemistry is useful when morphologic features are equivocal. Minimum markers that would help improve lymphoma diagnosis in our center would include CD20, CD3, and Bcl2 to differentiate a reactive process from a lymphoma, CD5, and CD23 to identify SLL seen in this study, CD15, and CD30 to confirm diagnosis of Hodgkin's lymphoma and Ki-67 to determine tumor grade which is useful for treatment planning.


  Conclusion Top


The majority of lymph nodes biopsied showed features of reactive lymphadenopathy, with the majority being nonspecific etiology. Among the lymphomas, NHL was seen more frequently with small lymphocytic lymphoma and DLBCL variants accounting for the majority. These findings are consistent with those of published literature. Due to the highly technical and challenging nature of lymph node pathology diagnosis, there is a need for specialist training in hematopathology as well as the establishment of well-equipped facilities for accurate and cost-effective diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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