|ORIGINAL RESEARCH REPORT
|Year : 2016 | Volume
| Issue : 2 | Page : 58-71
The challenges of lymphoma diagnosis in a Tertiary Hospital in Lagos, Nigeria
Olakanmi Ralph Akinde1, Charles Chidozie Anunobi1, Oluseye Vincent Osunkalu2, Adekoyejo Abiodun Phillips1, Olatunji Micheal Afolayan3
1 Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria
2 Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos, Lagos, Nigeria
3 Department of Surgery, College of Medicine, University of Lagos, Lagos, Nigeria
|Date of Web Publication||4-Apr-2016|
Olakanmi Ralph Akinde
Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos
Source of Support: None, Conflict of Interest: None
Background: In most tertiary centers across sub-Saharan countries, hematoxylin and eosin (H and E) stained slide is the main method of diagnosing lymphomas, and this has been found to be inadequate in diagnostic hematological malignancies. Aim and Objectives: To review the diagnostic utility and limitations of H and E, tissue diagnostic modality of solid hematolymphoid malignancies. Materials and Methods: The diagnosis based on both morphology and immunohistochemistry (IHC) assessments were compared with those based solely on morphology. Results: Of all, the 116 cases of lymphomas, only 32 (27.6%) were correctly diagnosed and subtyped by morphology while 53 (46%) cases were diagnosed to be lymphomas but could not be subtyped by morphology. Nineteen (16.4%) cases were wrongly subtyped. Five cases of reactive lesions were wrongly diagnosed as malignant lymphoma. Conclusion: This study makes a case for the mandatory use of IHC in the diagnosis of suspected cases of lymphomas.
Keywords: Challenges, diagnosis, immunohistochemistry, lymphoma, reactive lesions
|How to cite this article:|
Akinde OR, Anunobi CC, Osunkalu OV, Phillips AA, Afolayan OM. The challenges of lymphoma diagnosis in a Tertiary Hospital in Lagos, Nigeria. J Clin Sci 2016;13:58-71
|How to cite this URL:|
Akinde OR, Anunobi CC, Osunkalu OV, Phillips AA, Afolayan OM. The challenges of lymphoma diagnosis in a Tertiary Hospital in Lagos, Nigeria. J Clin Sci [serial online] 2016 [cited 2020 Mar 29];13:58-71. Available from: http://www.jcsjournal.org/text.asp?2016/13/2/58/179679
| Introduction|| |
Lymphomas are a heterogeneous group of neoplasms of lymphoid tissues, each with distinct clinicopathological features and varying response to treatment.
Although, the paucity of information on lymphoma in sub-Saharan Africa makes accurate estimates difficult, the finding of Ferlay et al.  indicated that of all the cancers occurring in sub-Saharan Africa, hematolymphoid malignancies have emerged as a major cause of morbidity and mortality with lymphomas and other hematologic malignancies such as leukemia and multiple myeloma together accounted for 8.7% of incident cancer diagnoses and 9.9% of cancer deaths in 2008. Annual incidence as low as 30,000 and as high as 278,000 of nonHodgkin lymphoma (NHL) have been reported in sub-Saharan Africa making it to be one of the most common cancers in the region. , Literature review showed that in most Nigerian Tertiary Hospitals, lymphomas, mostly NHL ranked among the leading cancers. ,,,,
The contemporary management of these neoplasms requires that they are accurately diagnosed, classified by sub-typing according to the WHO system of classification.  This classification is a multiparametric approach requiring clinical, morphological, immunological, cytogenetic, and molecular techniques. The impact of this has been reflected in the resource-rich settings where treatment of those malignancies is increasingly associated with unprecedented rates of long-term cure and control. The contemporary diagnosis of lymphoma remains a major challenge in sub-Saharan Africa, due to inadequate facilities, despite its perceived increase as a result of HIV endemicity in the region. 
In most tertiary centers across sub-Saharan countries, the only standard for tissue diagnosis is still the morphology of the cells as they appear under hematoxylin and eosin (H and E) stains of formalin fixed paraffin-embedded lymphoid tissue.  Although this is an important historic basic diagnostic modality, it is limited and cannot be used alone without other contemporary diagnostic modalities in lymphoma diagnosis and classification, even with special stains such as Giemsa, methyl green pyronin, reticulin periodic acid-Schiff which can neither differentiate B from T-cells nor be of prognostic/therapeutic markers.
The key findings of the international network for cancer treatment and research, which convened a panel that visited national referral hospitals in Nigeria, Kenya, Ghana Tanzania and Uganda to evaluate infrastructure for diagnosing lymphoma, indicated highly variable equipment and personnel as well as overused suboptimal fine needle aspiration specimen, variable turnaround time, variable histology and cytology preparations with lower standards than developed countries.  They reported on the nonexistence of immunohistochemistry (IHC), cytogenetics, and molecular and fluorescence in situ hybridization techniques, which are core elements in diagnostic hematopathology in developed worlds. Therefore, the tendencies for lymphoma over and missed diagnosis in those centers are unavoidably high.
Although morphology remains the cornerstone for the diagnosis of HL, the morphology complexity of NHL often hampers the pathologist's ability to differentiate benign from malignant disease correctly. , Histologic subtyping with the help of immunohistochemical characterization of the tumor cells has resulted in the level of distinction between lymphomas subtypes which were not previously possible. With the use of IHC reactive lymphoid lesions could be differentiated from malignant lymphomas with reactive pattern and poorly differentiated carcinomas, melanoma and sarcomas could also be differentiated from some anaplastic form of lymphomas. Lymphomas should be identified among the round blue cell tumors of childhood. Even within the lymphomas, the morphology heterogeneity and resemblance demand more than H and E, for diagnosis, classification and proper management. Today, the diagnosis and classification of lymphoma rely heavily on the determination of cell lineage, maturation, and function based on antigen expression as well as genetic analysis in addition to the morphology and clinical features. This has made IHC and cytogenetics become an integral part of diagnostic hematopathology and is required for the contemporary treatment, prognostication. and research. For this reason, many institutions often opt to engage the diagnostic services of foreign laboratories for lymphoma cases. However, this option is associated with the disadvantages of tissue loss in transit, delay in reporting, additional expense and does not enable learning opportunity.
In this study, our aim and objective are to review the utility and limitations of H and E, tissue diagnostic modality that is available for the diagnosis of lymphomas in our center as it occurs in most of the resource-poor laboratories in sub-Saharan Africa and to highlight the diagnostic utility of basic antibody panels that can be used to improve on the diagnostic limitations of H and E, assessment of solid hematolymphoid malignancies.
| Materials and methods|| |
This study is a retrospective study of 133 cases. Among these were 114 cases of malignant lymphoma, two cases of metastatic lesions and 13 cases of benign proliferative lesions but suspected for malignancy. These assessments were based on the morphologic features of the H and E, stained sections of formalin fixed paraffin embedded tissue in the Department of Anatomic and Molecular Pathology, Lagos University Teaching Hospital Lagos, Nigeria, between 2009 and 2012. Patient data were extracted from the case notes and request forms of the patients. The formalin fixed paraffin embedded tissue blocks and H and E, stained slides were selected, and each case was reviewed. New sections were made when the slides were not seen or suboptimal for assessment. The tissue blocks and slides were at different occasions sent for consultation at the Department of Cellular Pathology, Queen's Hospital, Rom Valley, Romford, Essex.
The impressions of the second opinion on those samples based on morphology and IHC were compared with our impression based on morphology alone. Using the diagnosis of the second opinion as standard, our diagnoses were categorized into one of the followings:
- Appropriately diagnosed as lymphoma subtype by morphology
- Those cases correctly diagnosed as lymphoma but could not be subtyped by morphology
- Diagnosed as lymphomas but inappropriately subtyped (named as a different type of lymphoma)
- Truly reactive lesions among the equivocally reactive cases
- Cases of equivocal reactive lesions which were diagnosed to be lymphoma by morphology and IHC
- Cases diagnosed to be lymphoma but turned out to be nonlymphomatous neoplasm
- Cases diagnosed to be nonlymphomas but turned out to be lymphoid malignancy
- Cases that were truly nonlymphoid malignancy.
| Results|| |
Of a total of 133 cases sent for the second opinion, only four could not be processed due to suboptimal tissue preservation. Among the remaining 129 cases, there were 116 cases of lymphomas, 13 cases of reactive lesions. Of the lymphomas, HL constituted 18 (15.5%) and NHL 98 (84.5%). The NHL was made up of 75 (76.5%) and 23 cases (23.5%) of B- and T-cell types of NHLs respectively. The HL were all of classical type, made up of six cases each of nodular sclerosis and mixed cellularity as well as three cases each of lymphocyte-depleted and lymphocyte rich. [Figure 1] shows the distribution of different types of lymphoma seen in this study whereas [Table 1] shows the distribution of the categories of lymphoma diagnoses by morphology alone against different types of lymphomas by morphology and IHC.
|Figure 1: The frequency distribution of various subtypes of lymphoma. DLBL = Diffuse large B-cell lymphoma, BL = Burkitt's lymphoma, FL = Follicular lymphoma, SLL = Small lymphocytic lymphoma, MCL = Mantle cell lymphoma, MZL = Marginal zone lymphoma, MALT = Mucosal associated lymphoid tissue, PLAS = Peripheral T cell lymphoma, PREB = Precursor B cell lymphoma, ALCL = Anaplastic large cell lymphoma, PTCL = Peripheral T-cell lymphoma, MF = Mycoses fungoides|
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Only 32 (27.6%) cases of suspected lymphomas were correctly diagnosed and subtyped by morphology. These were made up of six cases each of diffuse large B-cell lymphoma (DLBL) and small lymphocytic lymphoma (SLL), all the six cases of Burkitt's lymphoma (BL), one case of lymphoblastic lymphoma as well as 13 cases of classical HL made of nodular sclerosis Hodgkin's lymphoma (NSHL) (5), mixed cellularity Hodgkin's lymphoma (MCHL) (4) and two cases each of; lymphocyte rich Hodgkin's lymphoma/lymphocyte rich and lymphocyte depleted Hodgkin's lymphoma (LRHL and LDHL).
Fifty-eight cases were correctly diagnosed to be lymphomas but could not be subtyped by morphology alone. These were diagnosed by second opinion to be DLBL (17), SLL (6), follicular lymphoma (FL) (6), mantle cell lymphoma (MCL) (4), three cases each of marginal zone lymphoma and mucosal-associated lymphoid tissue lymphoma and five cases of precursor lymphomas of which T-cell type was 4. It also consists of 8 cases of peripheral T-cell lymphoma (PTCL), 3 mycoses fungoides (MF), two cases of MCHL, and one case of anaplastic large cell lymphoma (ALCL).
Nineteen cases of morphologically diagnosed lymphoma were wrongly subtyped. Among this group were DLBL (9) and one case each of ALCL, PTCL, Precursor T cell lymphoma (Prec-T), Mycosis fungoides (MF), Follicular lymphoma (FL), MCL, PL, SHL, LRHL and LDHL.
Five cases of reactive lesions by IHC were wrongly diagnosed to be malignant lymphoma. These were made of two cases of Castleman disease diagnosed to be SLL, two cases of reactive hyperplasia which were diagnosed as FL, and one case of chronic sclerosing sialadenitis diagnosed as HL.
Of the 13 cases of nonneoplastic lesions by H and E, morphology alone, eight cases were correctly diagnosed while five cases were wrongly diagnosed as lymphomas. The latter consists of four case of SLL which were diagnosed to be reactive (2) and tuberculous (2) and also one case of PTCL diagnosed as reactive lesions.
Two cases of lymphomas were wrongly diagnosed by morphology assessment to be metastatic carcinoma.
[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6],[Figure 7],[Figure 8],[Figure 9] and [Figure 10] shows the micrographs of the H and E, microscopy and IHC staining patterns of the various types of lymphomas seen in this study.
| Discussion|| |
The study showed that a low percentage (27.6%) of the lymphomas diagnosed by IHC could be correctly diagnosed by H and E, morphology alone. This diagnostic limitation with regards to lymphoreticular neoplasms buttresses the important role of IHC in addition to morphology in diagnostic hemato-oncology. This limitation is supported by reviewed literatures on lymphoma from various centers in sub-Saharan countries ,,,] as most lymphomas in these studies could not be classified. In the study of Jaffe et al., , it was observed that histologic appearance alone may not be a reliable indicator of immunologic markers. However, the importance of morphology in surgical pathology must be stressed as a good morphologic assessment is required for the selection of appropriate antibody panels for IHC assessment. When a lymphoid neoplasm presents with conventional morphological features both architecturally and typical cellular contents, aided by good tissue preservation and processing, morphology assessment could provide adequate and important diagnostic information that could lead to a correct diagnosis (Figures of Diffuse Large B cell lymphoma (DLBCL), FL, BL). This fact was demonstrated by this study with regards to all cases of the BL which were correctly diagnosed by morphology. The high diagnostic efficiency of morphology in BL could have been due to the facts that all the cases were of usual clinical presentation and conventional morphology. The morphologic appearance of its variants would have been associated with some diagnostic challenges that will require IHC. Cases of BL almost always demonstrate about 100% proliferation index and show positivity, in addition to the B-cell antigen, for CD10, BCL6 but are usually negative for CD5, CD23, and BCL2  [Figure 2]. It is suggested that cases with acceptable morphology with moderate but with strong reactivity to BCL2 should be classified in this category if the cells are positive for BCL6, CD10, and are MUM/IRF-4 negative.  The reactivity of the tumor cells to CD10 and BCL2 usually have a roughly reciprocal relationship in the two variants of BL.  CD43 serves to distinguish the two as it is almost always positive in Burkitt lymphoma and less than half the time in Burkitt like lymphomas. It was not possible to demonstrate the relationship of this tumor with Epstein-Barr virus (EBV) that have been documented to have an important role in its etiopathogenesis for a long time in the sub-Saharan Africa.  Only 6 (18.8%) out of a total number of 32 cases of DLBCL were successfully subtyped by histology while the majority (53%) could not be sub-typed. Jaffe et al.  in their study on morphologic sub-classifications of diffuse NHL showed that histopathologic sub-classification could correctly predict immunologic phenotype in only 61% of cases, suggesting that in such cases of lymphomas, histological appearance alone may not be a reliable indicator of immunologic surface markers. Therefore, IHC becomes essential in diagnosing any form of obviously malignant lymphoreticular lesions as mere lymphoma or NHL is of no therapeutic, prognostic or research relevance.
The common lymphomas, DLBL, FL, and SLL, could be conveniently diagnosed and classified at least using the criteria of the working formulation for clinical use which is mainly based on architectural pattern and cellular morphology.  The presence of LH cells in LPHL, RS or its variants in case of classical HL CHL and proliferation centers in SLL and follicular architecture in FL should permit an accurate diagnosis. In addition, in case of conventional DLBCL [Figure 3], correct morphological assessment is not impossible with the presence of diffusely disposed large cells with nuclei size larger than that of macrophages or to normal lymphocytes.  However, lymphoma diagnosis without IHC will not provide an evidence-based therapeutic and prognostic indicators for the disease.
Recognizing the malignant nature of diffuse large lymphoid cell proliferation usually does not pose diagnostic challenge, but distinguishing such from nonlymphoid neoplasms such as poorly differentiated carcinomas, melanomas and sarcomas as well as their correct sub-typing into a specific lymphoproliferative lesion such as DLBCL, ALCL, HL, anaplastic plasmacytoma, myeloid sarcoma, etc., which can present predominantly as large cell neoplasm, can be very challenging without IHC. The large proportion of DLBL (58%) that were diagnosed as lymphoma unspecified and those that were wrongly sub-typed (28%) are an indication of the limitation of H and E, microscopy alone in the definitive diagnosis of lymphoma in this study. The morphologic heterogeneity of DLBCL could cause diagnostic difficulty such as was seen in the three cases of the DLBL. The presence of significant population of immunoblasts and atypical large RS like cells could lead to the morphological interpretation of HL without IHC and even a times can be confused with a reactive lesion with fulminant immunoblastic proliferation as in infectious mononucleosis. Likewise, this morphological variance would explain the reason why nine cases of DLBCL were wrongly diagnosed as BL (two cases) and SLL (three cases), HL (3) and lymphoplasmacytic lymphoma (one case). In addition, this limitation will explain the case of suspected HL involving the parotid gland that was confirmed to be a chronic sialdenitis [Figure 4] due to the presence of distorted glands resembling atypical/Reed-Steinberg like cells. Therefore, because of the marked overlap in the cytologic features of lesions with large cell proliferation, IHC is essential for their definitive diagnosis.
Guided by the morphology and architectural pattern of the tumor cells, a small primary panel of antibody selection from LCA, CD3, CD20, CD79, CD10, CD15, CD30, BCL2, AE1/AE3, MIB 1, TdT, synatophisin, melan A, and sometimes a 2 nd panel of smaller markers such as PAX 5, MUM1, CD138, CD56, CD57, lysozyme, Alk 1, EMA will provide almost all important diagnostic clues to the cell type of the large cells. The positivity of the large cells for CD20/CD79a, a B lineage marker, supports the diagnosis of DLBCL [Figure 3] while its negativity may indicate ALCL and CH, although about 10-20% cases of CHL could be heterogeneous for CD20.  Also the positivity of the large cells for CD3 supported T-cell neoplasm like ALCL [Figure 5] or PTCL, though not commonly of large cell morphology. Although, most cases of the HL in this study were correctly diagnosed by morphology alone, three cases were wrongly diagnosed by morphology as DLBCL. The study identified the use of CD15 and CD30 to be complementary for the diagnosis of CHL as those cases of CHL that were negative for CD30 were CD15 positive [Figure 6]. CD30 positivity alone but with positivity for EBV will be in support of CHL rather than DLBCL or ALCL, which can be CD30 positive but rarely EBV positive. ,, The absence of NLPHL, a sub-type of HL with a favorable prognosis even after being transformed into DLBCL and HL, in rare occasions, is in agreement with the finding in literatures that it is not common, constituting about 2-7% of HL.  Clinical finding supported by morphology alone could be enough to make a clear-cut distinction between NLPHL and CHL. Differentiating NLPHL from CHL and T-cell/histiocytic riched DLBCL by IHC may necessitate the use of IHC for therapeutic purpose as LPHL is managed differently. ,
SLL constituted a large proportion among the lymphoma of small cell morphology sent for IHC and this could be explained by its higher frequency among lymphoma of small cell type and corroborates the fact that despite the presence of the usual morphology (fairly uniform tumor cells, presence of prolymphocytes, few immunoblasts, and regularity of the nuclear membrane) appropriate morphological diagnosis could be difficult. The presence of polymorphous small lymphoid infiltrates and absence of or indistinct prolymphocyte centers could constitute a pitfall in the diagnosis of SLL and it differentiation from PTCL and reactive lymphoid lesions. This could be responsible for the six cases of SLL that were recognized as lymphoma but were not typed. The positivity of the tumor cells for CD20, CD23, and CD5 is essential for the diagnosis of SLL [Figure 7]. Lymphoproliferative lesions with intense small cell infiltrate admixed intimately with large cells either in diffuse or expansible parafollicular hyperplasia could erroneously be viewed as a polymorphous infiltrate rather than being pleomorphic and hence diagnosed as reactive lesion as it occurred in four cases in this study. The expression of aberrant markers such as CD5, BCL2 and CD43 in B-cells usually and always indicate neoplasm rather than a reactive process [Figure 8]. This in addition to the presence of morphologic features in keeping with neoplastic lesions such as nuclear atypia, cytoplasmic clearing, polymorphism, follicles with the absence of mantle zone and indistinct sinuses should guide in diagnostic decision.  When a lymph node is partially involved in the neoplastic process or have a focus of necrosis, a polymorphous infiltrate may be seen. Although none of the SLL was wrongly diagnosed as DLBL, the presence of abundant para immunoblasts in SLL or viewing a small sample size with focal predominance of fairly large cells such as prolymphocytes and paraimmunoblasts which are usual accompaniments of SLL may mimic immunoblasts and hence an impression of DLBCL by the unwary.
On morphologic basis, making accurate diagnosis of follicular lymphoma should not pose much difficult task except in cases with unusual histologic appearance. However, lymphoid lesions could show barely discernible follicularity due to increase in the number of interfollicular centroblasts and centrocytes and intense T-lymphocytic infiltration thereby making it difficult differentiating malignant from reactive processes. An accurate diagnosis will require clarification by IHC [Figure 10]. Loss of immunoarchitecture of the lymph node due to alteration in the cellular components of the follicles, absence of polarity, absence of starry sky like appearance of tangible body macrophages and low mitotic activity will support the diagnosis of follicular neoplastic proliferations.  However, in the case of in situ FL, or partially involved lymph nodes, as seen in one of the unspecified lymphoma in this study, these features might not be convincing enough and hence giving an impression of a reactive lesion [Figure 11]. In children and in some reactive changes such as HIV, the mantle zone might also be attenuated creating an impression of a neoplastic lesion.
This study also showed the limitation of H and E, morphology alone in the diagnosis of MCL, as the four cases of MCL were diagnosed as small cell lymphomas unspecified and the only one specified was wrongly called SLL. Although MCL is seen as a low-grade lymphoma morphologically, it is a clinically aggressive lymphoma and these patients will not benefit from the therapeutic modalities of indolent lymphoma portrayed by the morphologic appearance of the cells. ,, Like SLL, MCL cells are known to display small cells but with oval or angulated nuclei, and usually of monotonous cell population that usually disposed in nodular pattern and show hyalinization of the blood vessels. However, in some cases owning to some intrinsic features of the tumor cells or poor fixation, the nuclei can be rounded like SLL. The reactivity of the tumor cells with cyclin D1, CD20, and CD23 is diagnostic of MCL [Figure 12].
From this study, there is no morphologic appearance that is pathognomonic of each of the various lymphomas with small cell morphology. Each of the tumors can display discrepancy in their conventional cellular appearances and be disposed in pseudo follicular, vague nodularity as well as diffuse and parafollicular patterns, thereby mimicking one another and sometimes difficult to differentiate from reactive lesions. IHC, as shown in this study, is an invaluable diagnostic means of sorting out these lymphomas. With the use of small panels from B-cell markers like CD20 or CD19, CD5, CD23, CD10, BCL2, BCL6, and cyclin D1 as well as CD43, the diagnostic dilemma associated with lymphomas of small B-cell variants could be solved to a very large extent. , SLL shows positivity with CD5 and CD23 but negative for CD10 and BCL6 which were positive for FL, while cyclin D1 will be positive in MCL but not in the previous two. The loss of normal immune-architecture and expression of aberrant B-cell markers such as CD5, CD43 and cyclin D1 as well as BCL2 in neoplastic proliferations are helpful in distinguishing them from benign lesions. ,,
The study showed that although the malignant nature of lymphoblastic lymphomas [Figure 13] was recognized by morphology in all the cases but the lesions could not be subtyped as B- or T-cell in origin because these two have subtle and subjective morphological differences. A panel of antibody consisting of CD3 (cyt), CD5, CD20/CD79a, and CD34, TdT, CD99 were useful to differentiate the cells into B- or T-cell types as well as to exclude mature lymphomas with morphological resemblance such as blastoid MCL, BL, and DLBCL. Immature B- and T-cell are positive for TdT and CD43 but the B-cell are usually negative for CD20 and CD45 while immature T-cell are surface CD3 negative. ,
Unlike the B-cell NHL, the study showed that, as already documented in the literature, the diagnosis and classification of T-NHL is more complicated by its diverse morphological types, extensive inflammatory background and nonspecific antigen profile as well as poor histogenesis of the tumor cells.  With the exception of ALCL and AIBL, most cases of nodal T-cell lymphomas are poorly defined and are categorized under a big umbrella called PTCL which constitutes about 50% of mature T-cell lymphomas as seen in this study. Out of the 10 cases of the PTCL, eight were suspected for lymphoma and two cases were misdiagnosed as tuberculosis and SLL. PTCL is a waste basket diagnosis where all types of T-cell lymphoma that could not be classified as an entity by clinical and morphological means are dumped, thereby accounting for its heterogenous morphology. The association of T-cell lymphomas with abundant mixed inflammatory background could lead to the diagnosis of a reactive lesion as seen in this study. The limitation of H and E, morphology alone in the diagnostic hematopathology was also reflected in the diagnosis of ALCL [Figure 4] as this could be misdiagnosed as HL or anaplastic carcinoma most probably due to the presence of atypical large cells. With a small panel of markers consisting of CD20, CD3, CD15, CD30 and cytokeratin, these tumors could be differentiated with ease. Positivity of the large cells for cytokeratin will exclude lymphoma while staining with CD3 often excludes HL as well as DLBCL. ,,, Occasionally, in addition to these, staining for Alk1 and EMA (ALCL positive), PAX5 and EBV (HL positive) might be required as the second panel if necessary. Additional antibody panel, consisting of CD4, CD8, CD7 as well as markers for cytotoxic granules (lysozyme, perforin, TIA, granzyme) might also be required in cases of T-cell lymphoma. The polymorphous morphology and presence of equivocal atypical small cell seen in most T-cell especially the PTCL might cause confusion between T-cell lymphomas and reactive lesions in which the reactive cell are predominantly T-cell response. Unlike diffuse B-cell proliferative lesions, where the loss of immuno architecture is usually in support of lymphoma, such diffuse T-cell proliferation can be seen in reactive lymphoid lesion with predominant T-cell infiltrate. In this case identification of loss of pan T-cell markers like CD2, CD3, CD5, CD7, or expression of aberrant markers such as ALK1, CD56 (in nodal lesions) as well as double negativity or positivity for CD4 and CD8 by the tumor cells are needed to exclude such reactive lesions. 
This study showed that among lymphoid lesions that can pose serious diagnostic challenge using morphology as the sole diagnostic tool is Castleman disease [Figure 14]. All the three cases seen in this study were not correctly diagnosed. This is most probably due to its nonconversant diagnostic features and less frequently due to the fact that it can mimic or be associated with lymphomas. The usual morphology of expanded mantle with onion skin pattern and presence of hyalinized vessels and plasma cells will assist in its diagnosis. The diagnostic accuracy can be improved with IHC as the follicules will be BCL2 negative and the mantle zone cells BCL2 positive. In addition, the plasma cell will show polyclonal immunoglobulin light chain.
| Conclusion|| |
This study demonstrated that, although morphology remains the cornerstone for the diagnosis of lymphomas, the morphologic complexity of NHL often hampers the pathologist's ability to differentiate benign from malignant disease correctly. Histologic subtyping with the help of immunohistochemical characterization of the tumor cells will help to distinguish between lymphomas subtypes, differentiate between reactive and nonreactive malignant lymphoid lesions and identify poorly differentiated malignant nonlymphoid neoplasms. We recommend that zonal centers should be established in resource poor countries such as Nigeria where facilities for accurate diagnosis of lymphomas are made available as this will improve therapeutic and prognostic values as well as enhancing contemporary researches in areas of lymphoreticular diseases.
We express our gratitude to Prof. AAF Banjo of The Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, the management of The Specialist Laboratory for allowing us to use their materials for this study and for their professional guide. We also acknowledged the consultancy services provided by Dr. Uche Igbokwe of The Department of Cellular Pathology, Queen's Hospital Rom Valley, United Kingdom.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
Kleihues P, Stewart BW. World Cancer Report. Lyon: International Agency for Research on Cancer Press; 2003. p. 237-41.
Giulia de F, Rogena EA, Naresh K, Rapheal M, Magrath I, Lorenzo L. Managing lymphomas in African setting: Improving diagnostic accuracy and carrying out research projects. Cancer Control 2013:75-82.
Anunobi CC, Banjo AA, Abdulkareem FB, Daramola AO, Akinde RO, Abudu EK. Adult lymphomas in Lagos Nigeria: A fourteen year study. Nig Q J Hosp Med 2007;17:63-6.
Oluwasola AO, Olaniyi JA, Otegbayo JA, Ogun GO, Akingbola TS, Ukah CO, et al
. A fifteen-year review of lymphomas in a Nigerian tertiary healthcare centre. J Health Popul Nutr 2011;29:310-6.
Omoti CE, Nwannadi AI, Obieche JC, Olu-Eddo AN. The epidemiological features of lymphoid malignancies in Benin city, Nigeria: A 15 years study. Pan Afr Med J 2012;11:10.
Yawale I, Weiqiang Z, Leona WA. Malignant lymphoma subgroup from Zaria, Nigeria, reveal absence of HIV/AIDS related plasmalastic lymhpmas and HHV-8 related lymphoproliferative disorders. Infect Agent Cancer 2010;5 Suppl 1:A54.
Babatunde A, Amiwero C, Olatunji P, Durotoye I. Pattern of Haematological Malignancies in Ilorin, Nigeria: A Ten Year Review. The Internet Journal of Hematology 2008;5:1-7.
Jaffe ES, Harris NL, Diebold J, Müller-Hermelink HK. World Health Organization classification of lymphomas: A work in progress. Ann Oncol 1998;9 Suppl 5:S25-30.
Gopal S, Wood WA, Lee SJ, Shea TC, Naresh KN, Kazembe PN, et al
. Meeting the challenge of hematologic malignancies in sub-Saharan Africa. Blood 2012;119:5078-87.
Naresh KN, Raphael M, Ayers L, Hurwitz N, Calbi V, Rogena E, et al
. Lymphomas in sub-Saharan Africa - What can we learn and how can we help in improving diagnosis, managing patients and fostering translational research? Br J Haematol 2011;154:696-703.
Jaffe ES, Strauchen JA, Berard CW. Predictability of immunologic phenotype by morphologic criteria in diffuse aggressive non-Hodgkin′s lymphomas. Am J Clin Pathol 1982;77:46-9.
Jaffe ES, Harris NL, Stein H, Isaacson PG. Classification of lymphoid neoplasms: The microscope as a tool for disease discovery. Blood 2008;112:4384-99.
Leoncini L, Raphael M, Stein H, Harris NL, Jaffe ES, Kluin PM. WHO Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissue. Lyon, France: International Agency for Research on Cancer Press; 2008. p. 262-4.
Christopher DG. Immunohistology of Non Hodgkin Lymphoma. Diagnostic Immunohistochemistry. 2 nd
ed. Philadelphia: Elsevier; 2006. p. 137-61.
Carbone A, Gloghini A, Aldinucci D, Gattei V, Dalla-Favera R, Gaidano G. Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin′s disease. Br J Haematol 2002;117:366-72.
Robb-Smith AH. U.S. National Cancer Institute working formulation of non-Hodgkin′s lymphomas for clinical use. Lancet 1982;2:432-4.
Stern H, Wernike RA, Clan WC, Jaffe ES, Chan JKC, Gatter KC et al
. WHO Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissue. Lyon, France: International Agency for Research on Cancer Press; 2008. p. 232-7.
Zukerberd LR, Collin AB, Ferry JA, Harris NL, Coexpression of CD 15 and CD20 by Reedsteinberg cells in Hodgkin disease. Am J Patho 1991;139:475-83.
Anagnostopoulos I, Hansmann ML, Franssila K, Harris M, Harris NL, Jaffe ES, et al
. European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: Histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes. Blood 2000;96:1889-99.
Jaffe ES. Anaplastic large cell lymphoma: The shifting sands of diagnostic hematopathology. Mod Pathol 2001;14:219-28.
Jaffe ES. Pathology of peripheral T cell lymphoma. Heamatology Am Soc Hematol Educ 2006;126:317-22.
Fraga M, Forteza J. Diagnosis of Hodgkin′s disease: An update on histopathological and immunophenotypical features. Histol Histopathol 2007;22:923-35.
Pinkus GS, Said JW. Hodgkin′s disease, lymphocyte predominance type, nodular - Further evidence for a B cell derivation. L & H variants of Reed-Sternberg cells express L26, a pan B cell marker. Am J Pathol 1988;133:211-7.
Pileri SA, Ascani S, Leoncini L, Sabattini E, Zinzani PL, Piccaluga PP, et al
. Hodgkin′s lymphoma: The pathologist′s viewpoint. J Clin Pathol 2002;55:162-76.
Fletcher Z, Chan JK, Tsanq WY. Pathology of lymph nodes. Contemporary Issues in Surgical Pathology. 3 rd
ed. New York: Churchill Livingstone; 1996. p. 81-167.
Norton AJ, Matthews J, Pappa V, Shamash J, Love S, Rohatiner AZ, et al
. Mantle cell lymphoma: Natural history defined in a serially biopsied population over a 20-year period. Ann Oncol 1995;6:249-56.
Bosch F, López-Guillermo A, Campo E, Ribera JM, Conde E, Piris MA, et al
. Mantle cell lymphoma: Presenting features, response to therapy, and prognostic factors. Cancer 1998;82:567-75.
Swerdlow SH, Williams ME. From centrocytic to mantle cell lymphoma: A clinicopathologic and molecular review of 3 decades. Hum Pathol 2002;33:7-20.
Watson P, Wood KM, Lodge A, McIntosh GG, Milton I, Piggott NH, et al
. Monoclonal antibodies recognizing CD5, CD10 and CD23 in formalin-fixed, paraffin-embedded tissue: Production and assessment of their value in the diagnosis of small B-cell lymphoma. Histopathology 2000;36:145-50.
Vasef MA, Medeiros LJ, Koo C, McCourty A, Brynes RK. Cyclin D1 immunohistochemical staining is useful in distinguishing mantle cell lymphoma from other low-grade B-cell neoplasms in bone marrow. Am J Clin Pathol 1997;108:302-7.
Yang WI, Zukerberg LR, Motokura T, Arnold A, Harris NL. Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia. Am J Pathol 1994;145:86-96.
Elenitoba-Johnson KS, Megan SL, Carl K. Mature T cell and NK neoplasms in Practical Diagnosis of Hematologic Disorders. 5 th
ed., Vol. 2: Chicago, IL; American Society for Clinical Pathology Press, 2010. p. 769-71.
Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al
. A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 1994;84:1361-92.
Soslow RA, Baergen RN, Warnke RA. B-lineage lymphoblastic lymphoma is a clinicopathologic entity distinct from other histologically similar aggressive lymphomas with blastic morphology. Cancer 1999;85:2648-54.
Borowitz MJ, Chan JC. WHO Classification of Tumors of Haematopoetic and Lymphoid Tissue. 4 th
ed. Lyon: International Agency for Research on Cancer Press; 2008. p. 167-78.
Wright DH, Anthony SY, Addis BJ, T Cell lymphoma in Diagnostic Lymph Node Pathology 1 st
ed. Vol. 1: Hodder Arnold, London; 2006. p. 91-115.
Chan JK. Peripheral T-cell and NK-cell neoplasms: An integrated approach to diagnosis. Mod Pathol 1999;12:177-99.
Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, et al
. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK ALCL and peripheral T-cell lymphoma, not otherwise specified: Report from the International Peripheral T-Cell Lymphoma Project. Blood 2008;111:5496-504.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14]