|Year : 2019 | Volume
| Issue : 1 | Page : 14-20
Clinicopathological, immunohistochemical charachtaristic and the outcome of Hodghkin lymphoma patients in Erbil city, Iraq
Lilan Bahzad Mohammedzaki1, Kawa Muhammedamin Hasan1, Ranan Kardagh Polus2, Ahmed Khudair Yassin1
1 Department of Clinical Hematology, Nanakali Hospital for Blood Diseases and Cancer, Irbil, Iraq
2 Department of Pathology, Collage Medicine, HMU, Irbil, Iraq
|Date of Submission||17-Feb-2018|
|Date of Acceptance||20-Sep-2018|
|Date of Web Publication||12-Feb-2019|
Dr. Lilan Bahzad Mohammedzaki
Nanakali Hospital for Blood Diseases and Cancer, Irbil
Source of Support: None, Conflict of Interest: None
BACKGROUND: Hodgkin lymphoma (HL) has unique epidemiological features with diversified pathologies and exhibits considerable clinicopathological variations in different parts of the world.
OBJECTIVES: We aimed in this study to assess clinic-pathological features, immunohistochemistry and outcome of HL patients treated in Erbil, northren Iraq.
PATIENTS AND METHODS: This was a retrospective study conducted in Nanakaly Hospital for blood diseases and oncology in Erbil, North Iraq; a total of 125 patients diagnosed between January 2012 and December 2016 were involved; they were assessed for their clinical characteristics and histopathology and immunophenotyping findings and their outcome was evaluated as well.
RESULTS: The median age was 28 years (range: 18–71 years); 55% were male and 41% had Stage II disease; common histological type is nodular sclerosis (51.2%) followed by mixed cellularity (43.2%); CD30 was positive in nearly all cases of classical HL, and CD15 was positive in 98.7% and CD20 was positive in 75% in nodular lymphocyte predominant subtype. Most of the patients received adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and the 5-year overall survival in our study is 70%. Advanced stage (IV), high lactate dehydrogenase level, low hemoglobin, and splenomegaly are significant predictors for poor survival.
CONCLUSION: Our patient exhibited outcomes that were lower to those reported in developed countries.
Keywords: Erbil, Hodgkin lymphoma, immunohistochemistry
|How to cite this article:|
Mohammedzaki LB, Hasan KM, Polus RK, Yassin AK. Clinicopathological, immunohistochemical charachtaristic and the outcome of Hodghkin lymphoma patients in Erbil city, Iraq. Iraqi J Hematol 2019;8:14-20
|How to cite this URL:|
Mohammedzaki LB, Hasan KM, Polus RK, Yassin AK. Clinicopathological, immunohistochemical charachtaristic and the outcome of Hodghkin lymphoma patients in Erbil city, Iraq. Iraqi J Hematol [serial online] 2019 [cited 2019 Jul 22];8:14-20. Available from: http://www.ijhonline.org/text.asp?2019/8/1/14/252133
| Introduction|| |
Hodgkin lymphoma (HL) is a B-cell-derived malignancy mostly affecting young adults. More than 80% of patients are cured after stage-adapted first-line treatment with chemotherapy and/or radiotherapy. It is an uncommon disorder with an annual incidence of 2–3/100,000 in Europe and the USA. In industrialized countries, the onset of HL shows a bimodal distribution with a first peak in the third decade and a second peak after the age of 50. Men are affected by HL slightly more often than women among all subtypes, except for the nodular sclerosing subtype that occurs slightly more often in young females than in male patients.
The usual presentation of HL is with painless lymph node (LN) enlargement. Constitutional symptoms may be present: “B” symptoms: fever above 38°C, drenching night sweats, and weight loss of more than 10% of baseline body weight. Detection of an unusual mass or swelling in the superficial, supradiaphragmatic LNs (60%–70% cervical and supraclavicular, 15%–20% axillary) is the most common presentation. There are two main types of HL, first is classical HL (cHL) which is further subdivided to (nodular sclerosis, mixed cellularity, lymphocyte predominant, and lymphocyte depleted) and second is nodular lymphocyte predominant HL (NLPHL). The immunophenotype and genetic features of both cHL and NLPHL have been defined. These are useful in the subclassification of HL and in distinguishing HL from two recently described, aggressive lymphomas that were in the past often diagnosed as HL: anaplastic large-cell lymphoma, T-cell type, and T-cell/histiocyte-rich large B-cell lymphoma.
Antibodies against CD15, CD30, and CD20 are often used to support morphological diagnosis of HL. The cHL is CD15+, CD30+, and CD20− in general and the NLPHL type is CD20+.
The staging system that is used in patients with HL is the Ann Arbor staging system. It divided HL into four stages (I–IV). Designations applicable to any stage (A) no symptoms, (B) fever (38°C), night sweats, and unexplained loss of 10% body weight in previous 6 months, (X) bulky disease, and (E) involvement of a single extranodal site that is contiguous or proximal to the known nodal site.
The prognostic scoring system was developed for patients with HL by the international prognostic score on advanced HL which includes anemia, lymphopenia, male sex, high erythrocyte sedimentation rate (ESR), age, and Stage III–IV. HL is a curable disease with 82%–90% of newly diagnosed patients achieving a durable remission with first-line therapy; however, 15%–20% of patients will be resistant to therapy (primary refractory) or relapse after treatment., A common treatment strategy for early-stage cHL is combined modality therapy with doxorubicin, adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by consolidative radiation therapy.
The aims of this study were to clinical presentation and stage of disease at presentation, histopathology and immunohistochemistry findings of LN biopsy, and finally, the outcome of the enrolled patients.
| Patients and Methods|| |
This is a retrospective study conducted in Nanakaly Hospital for blood diseases and oncology in Erbil city, Kurdistan Region of Iraq, on 125 patients diagnosed between January 2012 and December 2016. Patients aged ≥18 years diagnosed with HL biopsy and admitted to the hospital were included in this study; all patients aged below 18 years or those with missing data in the hospital were excluded from this study. Informed consent was obtained from included patients before accessing their files, and the study was approved by the Ethical Committee of the Kurdistan Board for Medical Specialties. Patients are mostly Kurds (second most ethnic groups in Iraq following Arab). All patients were diagnosed according to the WHO classification by tissue biopsy and confirmed by immunohistochemistry. Positron emission tomography–computed tomography (CT) or CT scan was performed to stage all patients according to the Ann Arbor staging system. The data were collected by reviewing their hospital file for age, sex, baseline hematological and biochemical investigations, organomegaly, type of HL, presence or absence of surface marker (CD15, CD30, CD20, and CD3), and bone marrow examination. Most of the patients in this study took adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD*6) or ABVD*8 as a treatment, and the 5-year overall survival (OS) was 70%.
Data were analyzed using the Statistical Package for the Social Science (SPSS 22, IBM, Armnok, NY, United State Of America). Chi-square test of association was used to compare proportions. Fisher's exact test was used when the expected count of more than 20% of the cells of the table was <5. Survival curves were plotted using the Kaplan–Meier method, and the log-rank test (by Mantel–Cox) was used to show whether there was a significant difference or not in the survival time of the study groups. P ≤ 0.05 was considered as statistically significant.
| Results|| |
The mean age (± standard deviation [SD]) of the patients was 32.57 ± 14.17 years (range: 18–71 years). The median was 28 years. More than half (53.6%) aged <30 years, and 55.2% of them were male with male-to-female ratio of 1:0.8.
The most commonly involved LNs were in the neck, mediastinum, and abdomen (80.8%, 68.8%, and 36%, respectively) as shown in [Table 1].
The mean hemoglobin (Hb) value ± SD was 12.01 ± 2.14 g/dl; 22.4% of the patients had low Hb. The mean white blood cell (WBC) counts were 11.46 ± 7.1315 × 109/l; 80.8% of patients had WBC count of <15 × 109/L. The mean lymphocyte count was 2.05 ± 1.11 × 109/L; 92.8% had lymphocyte count more than 0.6 × 109/L; the detail laboratory and bone marrow finding showed in [Table 2].
The CD expression was as follows: CD30 (96.8%), CD15 (95.2%), CD20 (3.2%), and CD3 (3.2%).
The CD15 expression was low (25%) in the nodular lymphocyte predominant, while it was more than 95% in the other types (P = 0.001) as presented in [Table 3]. The same pattern is observed in the same table regarding CD30 (P < 0.001). CD20 mostly expressed in the nodular lymphocyte predominant (75%), while it was 1.6% in the nodular sclerosis and 0% in the other types (P < 0.001). Nearly, the same pattern was observed regarding CD3 (P = 0.013).
[Table 4] shows that the more advance the stage of HL, the more the death rate within the period of 5 years, reaching to 30.4% in Stage 4 (P = 0.007). No significant difference was detected between the death rates of different types of HL (P = 0.433). The death rate (20.2%) was significantly higher among those with B symptom than the death rate (0%) among those with no B symptoms (P = 0.002). It was also higher among those with splenomegaly (32.3%) compared with 7.4% among those with no splenomegaly (P = 0.001). No significant association was detected between death rate and hepatomegaly (P = 0.123). The death rate was significantly (P < 0.001) high among those with Hb ≤10.5 (35.7%) than those with high Hb >10.5 (7.2%). No significant association was detected between death rate and WBCs > or < 15 × 109 (P > 0.99), lymphocytes ≤ or >0.6 × 109 (P > 0.99), and ESR equal > or <30 (P = 0.391). The death rate was significantly (P = 0.001) high among those with lactate dehydrogenase (LDH) ≥450 (33.3%) compared with 7.4% among those with LDH <450. Death rate was not associated with bone marrow involvement (P = 0.137).
|Table 4: Death rate according to clinical and laboratory characteristics|
Click here to view
This study shows that 103 out of 125 patients (82.4%) got remission, while 14 out of 125 patients (11.2%) had relapse. Most common treatment regimen used was ×6 ABVD, whether alone (54.4%) or in combination with ×6 Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone (BEACOPP) (5.6%), and only 8 patients underwent autologous stem cell transplant due to relapse [Table 5], due to relapse refractory disease.
[Figure 1] shows that mean OS time ± standard error was 60.76 ± 2.61 months. [Table 6] and [Figure 2] show that the mean survival time of males (58.25 months) does not significantly (P = 0.347) differ from that of females (56.67 months). [Figure 3] shows that the least survival time was in Stage 4 (P = 0.028).
|Figure 2: Mean overall survival time (months) by gender. Mean survival time ± standard error: 60.76 ± 2.61 month|
Click here to view
|Figure 3: Mean overall survival time (months) by stage of the disease. Log rank (Mantel–Cox): P =0.028. Note: The detailed table can't be computed|
Click here to view
| Discussion|| |
The distribution of disease was found to be more common in male, and the most common subtype of HL in our study was nodular sclerosis followed by mixed cellularity (51%,43% respectively), close figure were reported in study done in Dahouk and Sulaimanya in North part of iraq, and neighboring countries like Jordan, United Arab Emirate and Saudi Arabia, also close to our result were found in study done in USA.,,,,
In our study, NLPHL type, which is now considered as a distinct entity of HL according to the recent WHO classification system, was diagnosed in only 4 patients (3.2%); similar to this, 5% was also reported in study conducted in number of European and American center.
The median age at time of diagnosis was 28 years, 41.6% were in Stage II, and 28% of them were in Stage III; in comparison to the study done in USA, most of patients at the time of diagnosis were in stage II (40%) while (23%) were in stage I and this due to the fact of the availability of advanced facilities and imaging study for early detection and diagnosis of the disease.
Similar to our figures were reported in developing country like Nigeria and India which most of their patients were in stage III, IV at time of diagnosis.,
Most common nodal involvement in our study was in the neck (80%) followed by mediastinum (68%) (Saudi Arabia 65% in the neck followed by 7% mediastinum) and splenomegaly (24%) similar to a study done in Poland in which splenomegaly was found in 24%. B symptoms are present in 67% which is similar to other study (Egypt 61% and Saudi Arabia 82%).,
In the current study, CD30 was positive in nearly all cases of HL (96.8%), and this is similar to study done in North of Iraq, Egypt, and China (100%, 100%, and 100%, respectively),,, while CD15 was positive in 95% lower than other study, and this may be due to the properties of different antibodies, variation in the technique of incubation, and antigen retrieval.
CD20 was positive only in one case of cHL (1.6%) which is also lower than that reported in Egypt, China, and Austria (15%, 30%, and 20%, respectively),,, while three out of four cases of NLPHL were positive for CD20.
The 5-year OS in our study is 70% which somewhat similar to the study done in Mediterranean basin in Turkey (69%), Libya (59%) but our result showed to be lower when compared to studies done in France, Spain and USA which showed 5-year OS are (83%,86%, 85.2% respectively),, this difference in OS curve with the developed country may be due to first: delay at diagnosis which most of our patient seeking medical attention late, second: may be difference in modality of treatment and radiotherapy and third: may be due to short follow-up period in this study.
In the present study, advanced stage (IV), high LDH level, low Hb, and splenomegaly are significant predictors for poor survival. Other variables such as total leukocyte count, absolute lymphocyte count, and bulk disease were not predictors for survival, and this was similar to multivariate analysis of single institution. Most common cause of death in this study was due to the disease progression.
No statistical difference was found in OS between males and females which is similar to study published in 2011 on European patients with HL.
| Conclusion|| |
In this study, we have discussed in detailed the various clinical and histopathological parameters of HL; the most common type was nodular sclerosis, most of them were in Stage II–III, and most common LN involved was in the neck; 60% of patients had B symptom. Almost all patients had CD30 and CD15 positive by immunophenotyping.
In this study, advanced stage (IV), high LDH level, low Hb, and splenomegaly are significant predictors for poor survival, and the 5-year OS was 70%, which is lower than the developed country.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Eichenauer DA, Engert A. The evolving role of targeted drugs in the treatment of Hodgkin lymphoma. Expert Rev Hematol 2017;10:775-82.
Thomas RK, Re D, Zander T, Wolf J, Diehl V. Epidemiology and etiology of Hodgkin's lymphoma. Ann Oncol 2002;13 Suppl 4:147-52.
Harris NL. Hodgkin's lymphomas: Classification, diagnosis, and grading. Semin Hematol 1999;36:220-32.
von Wasielewski R, Mengel M, Fischer R, Hansmann ML, Hübner K, Franklin J, et al.
Classical Hodgkin's disease. Clinical impact of the immunophenotype. Am J Pathol 1997;151:1123-30.
Gospodarowicz MK. Hodgkin's lymphoma – Patient's assessment and staging. Cancer J 2009;15:138-42.
Ansell SM. Hodgkin lymphoma: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol 2012;87:1096-103.
El-Galaly TC, d'Amore F, Mylam KJ, de Nully Brown P, Bøgsted M, Bukh A, et al.
Routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography/computed tomography-staged treatment-naive patients with Hodgkin lymphoma. J Clin Oncol 2012;30:4508-14.
Cuccaro A, Bartolomei F, Cupelli E, Galli E, Giachelia M, Hohaus S, et al.
Prognostic factors in Hodgkin lymphoma. Mediterr J Hematol Infect Dis 2014;6:e2014053.
Milgrom SA, Pinnix CC, Chuang H, Oki Y, Akhtari M, Mawlawi O, et al.
Early-stage Hodgkin lymphoma outcomes after combined modality therapy according to the post-chemotherapy 5-point score: Can residual pet-positive disease be cured with radiotherapy alone? Br J Haematol 2017;179:488-96.
Yaqo RT, Hughson MD, Sulayvani FK, Al-Allawi NA. Malignant lymphoma in Northern Iraq: A retrospective analysis of 270 cases according to the World Health Organization classification. Indian J Cancer 2011;48:446-51.
] [Full text]
Haddadin WJ. Malignant lymphoma in Jordan: A retrospective analysis of 347 cases according to the World Health Organization classification. Ann Saudi Med 2005;25:398-403.
] [Full text]
Castella A, Joshi S, Raaschou T, Mason N. Pattern of malignant lymphoma in the united Arab emirates – A histopathologic and immunologic study in 208 native patients. Acta Oncol 2001;40:660-4.
Shafi RG, Al-Mansour MM, Kanfar SS, Al Hashmi H, Alsaeed A, Al-Foheidi M, et al.
Hodgkin lymphoma outcome: A Retrospective study from 3 tertiary centers in Saudi Arabia. Oncol Res Treat 2017;40:288-92.
Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS, et al.
Lymphoma incidence patterns by WHO subtype in the united states, 1992-2001. Blood 2006;107:265-76.
Diehl V, Sextro M, Franklin J, Hansmann ML, Harris N, Jaffe E, et al.
Clinical presentation, course, and prognostic factors in lymphocyte-Predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: Report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease. J Clin Oncol 1999;17:776-83.
Evens AM, Antillón M, Aschebrook-Kilfoy B, Chiu BC. Racial disparities in Hodgkin's lymphoma: A comprehensive population-based analysis. Ann Oncol 2012;23:2128-37.
Maddi RN, Linga VG, Iyer KK, Chowdary JS, Gundeti S, Digumarti R, et al.
Clinical profile and outcome of adult Hodgkin lymphoma: Experience from a tertiary care institution. Indian J Med Paediatr Oncol 2015;36:255-60.
] [Full text]
Olu-Eddo AN, Omoti CE. Hodgkin lymphoma: Clinicopathologic features in Benin City, Nigeria and update on its biology and classification. Niger J Clin Pract 2011;14:440-4.
] [Full text]
Sawan A, Al-Sayes FM. Clinico-pathological study of Hodgkin's disease in king Abdulaziz University hospital, Jeddah. J Taibah Univ Med Sci 2006;1:48-56.
Smolewski P, Robak T, Krykowski E, Blasiñska-Morawiec M, Niewiadomska H, Pluzanska A, et al.
Prognostic factors in Hodgkin's disease: Multivariate analysis of 327 patients from a single institution. Clin Cancer Res 2000;6:1150-60.
Allah HG, El Azzazi MO, Elafifi AM, Hegab HM, Moussa MM, Mostafa NN, et al.
Treatment outcome in Egyptian lymphoma patients, 2-year results, single-center experience. Egypt J Haematol 2014;39:209-16. [Full text]
Fadhil MS, Al-Nueimy WM, Lazim AF. Hodgkin's lymphoma. An immunohistochemical profile in Northern Iraq. Saudi Med J 2014;35:448-53.
Audouin J, Diebold J, Nathwani B, Ishak E, Maclennan K, Mueller-Hermelink HK, et al.
Epstein-Barr virus and Hodgkin's lymphoma in Cairo, Egypt. J Hematop 2010;3:11-8.
Fu XH, Wang SS, Huang Y, Xiao J, Zhai LZ, Xia ZJ, et al.
Prognostic significance of CD20 expression in Hodgkin and reed-Sternberg cells of classical Hodgkin's lymphoma. Ai Zheng 2008;27:1197-203.
Tzankov A, Krugmann J, Fend F, Fischhofer M, Greil R, Dirnhofer S, et al.
Prognostic significance of CD20 expression in classical Hodgkin lymphoma: A clinicopathological study of 119 cases. Clin Cancer Res 2003;9:1381-6.
Salati M, Cesaretti M, Macchia M, Mistiri ME, Federico M. Epidemiological overview of Hodgkin lymphoma across the Mediterranean Basin. Mediterr J Hematol Infect Dis 2014;6:e2014048.
Brenner H, Gondos A, Pulte D. Ongoing improvement in long-term survival of patients with Hodgkin disease at all ages and recent catch-up of older patients. Blood 2008;111:2977-83.
Marcos-Gragera R, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Maynadie M, et al.
Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: Results of the HAEMACARE project. Haematologica 2011;96:720-8.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]