Limfoma Hodgkin
Introduction and Facts
Hodgkin's lymphoma (LH) is a malignant disease affecting B-cell lymphocytes. It is characterized by Reed Sternberg cells against a background of pleomorphic inflammatory cells (lymphocytes, eosinophils, neutrophils, plasma cells, and histiocytes).
The Reed Sternberg cell is a very large cell with about 15 to 45 micrometers, a large multilobular nucleus with many prominent daughter nuclei, and slightly eosinophilic cytoplasm. The main characteristic of the Reed Sternberg cell is the presence of two adjacent nuclei, each containing a large, inclusion-like acidophilic daughter nucleus surrounded by clear cell regions. These morphological features make Reed Sternberg cells look like owl eyes. As many as 40% of lymphomas in adults are reported as LH. The incidence of LH is stable, with approximately 8,490 new cases reported in the United States in 2010. LH is more common in men than women (1,2:1) and is more common in whites than blacks. The age distribution in LH is bimodal with the first peak age, which is around 15 to 34 years, and the second peak age, which is about 50 years.
Pathophysiology
The exact cause of Hodgkin's lymphoma (LH) is still unknown. Still, several factors, such as exposure to viral infections, familial factors, and immunosuppression, are thought to be associated with the occurrence of LH. In 70% or one-third of reported cases of LH worldwide, the involvement of Epstein-Barr virus (EBV) infection in Reed-Sternberg cells is confirmed.
The gene expression of EBV is thought to trigger the transformation and reprogramming of B-cell lymphocytes to one of the LH phenotypes. At the time of primary infection, EBV will enter the latent phase in the memory of B-cell lymphocytes so that EBV can survive throughout the life span of B-lymphocytes. EBV then encodes the gene products EBNA-1 and LMP-1, which are thought to play a role in the memory transformation process of B-lymphocytes. These gene products act on intracellular signaling pathways where EBNA-1 affects negative feedback on tumor suppressor gene expression and enhances tumor progression through positive feedback on CCL22 which then promotes B-cell activation of lymphocytes. At the same time, the LMP-1 gene product mimics the signal generated by CD40, which acts to activate the NF-kB, p38, PI3K, AP1, and JAK-STAT signaling pathways in promoting B-cell survival of lymphocytes. EBV infection is also thought to be the cause of genetic mutations in the Ig gene encoding the B-cell receptor for lymphocytes, where EBV then encodes the LMP-2 gene, which can reprogram mature B-cell lymphocytes into one of the LH phenotypes and prevent the process of apoptosis through activation of salvage signals in B-lymphocyte germinal centers.
The series of processes mentioned above causes an uncontrolled clonal expansion of B-lymphocytes, secrete various cytokines, such as IL-5, which will attract and activate eosinophils, and IL-13 can stimulate Reed-Sternberg cells more, further to express CD30 (Ki-1) and CD15 (Leu-M1). CD30 is a marker of lymphocyte activation expressed by reactive and malignant lymphoid tissue cells. At the same time, CD15 is a marker of activated granulocytes, monocytes, and T-lymphocytes that B-lymphocytes do generally not express. People with a family history of LH, mainly twins, and people with compromised immune systems, such as HIV/AIDS, also have a high risk of developing LH.
Clinical Symptoms and Complications
Symptoms that are often found in patients with lymphoma are generally non-specific, including:
1. Weight loss >10% in 6 months
2. Fever 38 degrees C >1 week for no apparent reason
3. Night sweats a lot
4. Get tired quickly
5. Decreased appetite
6. Enlarged lymph nodes involved
7. A painless lump in the neck, armpit, or groin (especially if the size is more than 2 cm); or shortness of breath due to enlarged mediastinal lymph nodes or splenomegaly. The first three symptoms must be watched out for because they are associated with an unfavorable prognosis and bulky disease (KGB > 6-10 cm or mediastinum > 33% of the thoracic cavity).
According to the Lymphoma International Prognostic Index, clinical findings that affect the prognosis of patients with LH are age >60 years, involvement of both sides of the diaphragm or extranodal organs (Ann Arbor III/IV) and multifocality (>4 locations).
Although Hodgkin's Lymphoma can show a variety of symptoms, the common ones are:
• Prolonged and recurrent fever (frequent relapses)
• Unexplained weight loss
• Swollen lymph nodes that are palpable in the neck, armpits, and groin area
• Night sweats
• Loss of appetite
Having these symptoms does not necessarily mean that a person has lymphoma. These symptoms may also not be due to cancer. However, people who experience these symptoms should see a doctor to be properly diagnosed and treated if necessary.
Diagnosis
The diagnosis of Hodgkin's lymphoma (LH) is carried out by considering the findings obtained during history taking, physical examination, and supporting examination of the patient.
1. History.
a. Constitutional symptoms consisting of:
a) Symptoms B consisting of weight loss of more than 10% in the last six months, fever of more than 380C, and night sweats.4,7,10
b) Pel-Ebstein fever, which is a high fever for 1 to 2 weeks, then there is an afebrile period for 1 to 2 weeks, then the high fever reappears.
c) Pruritus is itching in part or all of the body.
d) Pain that arises in the spleen area after drinking alcohol.
b. Chest pain, coughing, shortness of breath, and back pain or bone pain.
c. Family history of the same disease, especially in nodular sclerotic LH.
2. Physical Examination.
a. Asymptomatic lymphadenopathy, painless enlargement of lymph nodes, is usually asymmetrical with a dense, rubbery consistency. The preference for lymph nodes that are typically involved is the neck (60-70%), axillary (10-15%), inguinal (6-12%), mediastinal (6-11%), hilar lung, para-aortic glands, and lymph nodes retroperitoneal.
b. Splenomegaly and hepatomegaly but rarely massive.
c. Superior vena cava syndrome with signs and symptoms in the form of distension of the neck veins and chest wall, edema of the face and upper extremities, shortness of breath, and headache in patients with massive mediastinal lymphadenopathy.
3. Supporting Examination.
a. Hematologic examination revealed anemia, neutrophilia, eosinophilia, lymphopenia, elevated erythrocyte sedimentation rate and LDH (serum lactate dehydrogenase).
b. Imaging examination, can find radiopaque images of unilateral or bilateral nodules that are not well-defined or well-defined and consolidation on chest radiography with Posterior Anterior (PA) projections; Hyperdense picture of multiple soft tissue masses due to nodule aggregation on CT scan with contrast in the thorax, abdomen or pelvis.
c. Histopathological examination revealed the presence of Reed Sternberg cells against a background of pleomorphic inflammatory cells on lymph node biopsy examination.
d. Immunohistochemical examination, can be found markers CD15, CD20, or CD30 in Reed Sternberg cells.
e. Other tests, such as liver, kidney and lung function tests, echocardiography and electrocardiography, are used to detect signs and symptoms of involvement of organs other than lymph nodes and pregnancy tests in young women.
Management and Treatment
Hodgkin's lymphoma (LH) management varies according to the type and stage, with treatment modalities consisting of radiotherapy, chemotherapy, and combination therapy. EORTC (European Organization for Research and Treatment of Cancer) classifies patients with classic LH into three stages based on criteria consisting of LH stage with the presence or absence of risk factors
Early-Stage Favorable
Early-stage favorable classical LH treatment was performed by administering ABVD chemotherapy regimen (Adriamycin 25 mg/m2, IV, day 1 and 15; Bleomycin 10 mg/m2, IV, day 1 and 15; Vinblastine 6 mg/m2, IV , days 1 and 15; Dacarbazine 375 mg/m2, IV, days 1 and 15) in 2 cycles followed by 20 Gy of radiotherapy.
Early-Stage Unfavorable
Classic early-stage unfavorable LH was treated with ABVD chemotherapy regimen (Adriamycin 25 mg/m2, IV, days 1 and 15; Bleomycin 10 mg/m2, IV, days 1 and 15; Vinblastine 6 mg/m2, IV, days 1 and 15; Dacarbazine 375 mg/m2, IV, days 1 and 15) in 4 cycles followed by radiotherapy of 30 Gy. Other, more intensive management is the administration of BEACOPP chemotherapy regimen (Bleomycin 10 mg/m2, IV, days 1 and 8; Etoposide 200 mg/m2, IV, days 1 to 3; Adriamycin 35 mg/m2, IV, day 1; Cyclophosphamide 1250 mg/m2, IV, day 1; Oncovin 1.4 mg/m2, IV, days 1 and 8; Procarbazine 100 mg/m2, orally, days 1 to 7; Prednisone 40 mg/m2, orally, days 1 to 14 with increasing doses in 2 cycles and followed by chemotherapy regimen of ABVD in 2 cycles and radiotherapy of 30 Gy.
Advanced-Stage Disease
Management of classic advanced-stage disease LH is carried out by administering chemotherapy regimens of ABVD or BEACOPP in 6 to 8 cycles and followed by radiotherapy if the lymphoma size is > 1.5 cm after administration of chemotherapy regimens of ABVD or > 2.5 cm after administration of chemotherapy regimens of BEACOPP.
LH type nodular lymphocyte-predominant
The management of the nodular lymphocyte predominant type of LH differs from the classical LH treatment because this type of LH has different biological characteristics from classical LH because of the presence of CD20. In patients with stage IA without any risk factors, lymph node removal can be performed, followed by watchful waiting or radiotherapy. In patients with more advanced settings, chemotherapy regimens of ABVD combined with Rituximab can be administered.
Reference:
1. Maya IPGNI, Rasmawati NLM. Hodgkin's lymphoma [Internet]. 2017 [cited 2021 Aug 27]. Available from: https://simdos.unud.ac.id/uploads/file_penelitian_1_dir/c52b9761d6e8ade70f0502c2708381b5.pdf
2.Parkway Cancer Centre. Hodgkin's lymphoma [Internet]. [cited 2021 Aug 27]. Available from: https://www.parkwaycancercentre.com/docs/default-source/cancer-types-pdfs/Bahasa/pcc_hodgkinlymphoma_bah.pdf?sfvrsn=f678a1e5_2
