|Year : 2022 | Volume
| Issue : 1 | Page : 60-62
A rare clinical presentation of Hodgkin's disease
Prashanth Parameswaran1, Dilip Harindran Vallathol1, Narayanankutty Warrier1, Sajna V Kutty2
1 Department of Medical Oncology, MVR Cancer Centre and Research Institute, Kozhikode, Kerala, India
2 Department of Pathology, MVR Cancer Centre and Research Institute, Kozhikode, Kerala, India
|Date of Submission||14-Dec-2020|
|Date of Decision||22-Jun-2021|
|Date of Acceptance||11-Jul-2021|
|Date of Web Publication||28-Apr-2022|
Dr. Prashanth Parameswaran
Department of Medical Oncology, MVR Cancer Centre and Research Institute, Kozhikode, Kerala
Source of Support: None, Conflict of Interest: None
Hodgkin's disease or Hodgkin's lymphoma (HL) is a hematolymphoid neoplasm of B-cell lineage that has unique histologic, immunophenotypic, and clinical features. The occurrence of hemophagocytic lymphohistiocytosis (HLH) and neurological symptoms is rare in this disease. We present a case report of a 40-year-old woman who presented to our outpatient department with HLH and cerebellar signs. On further investigations, she was found to have classical HL. Her clinical condition improved with one cycle chemotherapy and steroids and she is on follow-up. This case indicates that a strong index of clinical suspicion is key to diagnose HLH and neurological symptoms (probably paraneoplastic) in HL. The cornerstone of management is identifying and treating the underlying cause.
Keywords: Hemophagocytic lymphohistiocytosis, Hodgkin's lymphoma, neurological, paraneoplastic
|How to cite this article:|
Parameswaran P, Vallathol DH, Warrier N, Kutty SV. A rare clinical presentation of Hodgkin's disease. J Appl Hematol 2022;13:60-2
| Introduction|| |
Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening syndrome of excess immune activation. HLH may occur as a primary or acquired disorder, with the former occurring primarily in children with inherited immune deficiencies. Acquired, or secondary HLH, is typically seen in adults and commonly associated with malignancy, infection, and rheumatological disorders. Principal signs and symptoms of HLH include fever, splenomegaly, cytopenia, generalized malaise, and fatigue. Currently, the diagnosis of HLH is based on the following criteria: molecular identification of an HLH-associated gene mutation or five of the following eight findings: fever, splenomegaly, cytopenia affecting at least two of three lineages in the peripheral blood, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis in bone marrow, spleen, or lymph nodes, low or absent NK cell activity, hyperferritinemia, and high levels of soluble interleukin-2 receptor. Moreover, the occurrence of neurological symptoms as a part of this disease is also uncommon.
Here, we report a rare case of a middle-aged woman who presented with HLH and neurological symptoms and was diagnosed to have Hodgkin's disease (HD).
| Case Report|| |
Written and informed consent has been taken from the patient before treatment of this patient. No other identifiable information has been provided in the case report except for the age.
A 40-year-old woman with no comorbidities was evaluated for pyrexia of unknown origin for 2 months' duration. She was investigated outside computed tomography (CT) scan which showed supradiaphragmatic and infradiaphragmatic lymphadenopathy, hepatomegaly, and focal lesions in the spleen. She developed slurring of speech and difficulty in walking and difficulty in getting up when she presented to us and hence was admitted.
On examination, her Eastern Cooperative Oncology Group performance status was two and was tachypneic. She had intention tremors, dysmetria, and hepatosplenomegaly on per abdomen examination.
Routine blood investigations revealed a picture of pancytopenia. Positron emission tomography (PET) CT scan was taken which showed hypermetabolic left level four cervical, mediastinal, and retroperitoneal lymph nodes, minimal pericardial effusion, mild splenomegaly, and diffuse hypermetabolism in the marrow of visualized skeleton. Magnetic resonance imaging brain with contrast was taken in view of neurological symptoms, which showed T2/fluid-attenuated inversion recovery hyperintense symmetrical signals with reduced diffusivity in the central pons, without any enhancement/mass effect with a possibility of central pontine myelinolysis.
Her left cervical lymph node biopsy and immunohistochemistry were done which came back to be classic Hodgkin's lymphoma (HL) [Figure 1]. In view of conspicuous bone marrow findings in PET CT scan and cytopenias, bone marrow aspiration and biopsy were done. It showed a picture of HLH [Figure 2] and further immunohistochemical studies on marrow biopsy revealed involvement by HD [Figure 3]. Her serum ferritin was markedly elevated and triglycerides were also above the upper limit of normal. Her cerebrospinal fluid (CSF) cytology was negative, and CSF autoantibody panel (for ruling out paraneoplastic involvement) was negative.
|Figure 2: Bone marrow aspirate showing hemophagocytic lymphohistiocytosis|
Click here to view
She was started on corticosteroids as per the required dose. Concomitantly, she was commenced on adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) regimen for HL. Her cerebellar signs became normal and her counts also recovered after the first cycle. She has currently completed two cycles of ABVD, and her PET CT scan shows a complete metabolic response with Deauville score one. She has currently completed her treatment and is on regular follow-up.
| Discussion|| |
HLH is a disease that results from severe unchecked immune activation; it is associated with multiorgan damage and high morbidity and mortality. Defective granule-mediated cytotoxicity is considered to be the main pathophysiology in primary and secondary HLH. The association between HLH and hematologic malignancies including HL is well described, with 1% of these patients developing HLH. Perforin and Fas play an important role in T-cell and dendritic homeostasis, and loss of their function might lead to unchecked inflammation in HLH. The defect in these systems might also explain the strong association described between HLH and opportunistic infections.,
This is one of the very few case reports of HD presenting with HLH and central nervous system (CNS) involvement concurrently. Our patient had six findings which are consistent with the diagnosis of HLH – cytopenia, hyperferritinemia, bone marrow showing hemophagocytosis, fever, mild splenomegaly, and triglyceride above the upper limit of normal. Our patient had met both major and minor criteria to diagnose HLH. In our patient, HLH was most likely triggered by the tumor and infectious agents, probably Epstein–Barr Virus (EBV) related, which is a common association with HD. EBV titer could not be done for this patient for confirmation.
Cerebellar involvement in our case may be related to paraneoplastic involvement by HL or as a secondary manifestation of HLH. Primary CNS involvement by HL is very rare. There is a strong association between the circulating antineuronal antibody anti-Tr with paraneoplastic cerebellar degeneration and HL. Unlike other paraneoplastic syndromes in which the paraneoplastic syndrome precedes the diagnosis of cancer, the paraneoplastic disorder of HL usually begins after the diagnosis of HL or when the patient is in remission. Although we did a CSF panel, we could not perform the anti-Tr antibody test in CSF which is associated with HD. Other antibodies such as mouse metabotropic glutamate receptor (mGLuR1) and anti N methyl D aspartate receptor antibodies have also been associated with patients of HD. HLH-related CNS manifestations may be induced by CNS-related inflammatory cytokine storm or secondary to infection, especially EBV related. In retrospect, as the cerebellar signs disappeared with chemotherapy, it may be attributed to the paraneoplastic involvement of CSF by HD rather than HLH which usually is treated by intrathecal chemotherapy and has a more dismal outcome.,
Mainstay of the treatment of patients with secondary HLH is the underlying cause. High doses of glucocorticoids are typically used. Antibiotics, antiviral drugs, and intravenous immunoglobulin are often administered to combat opportunistic infections. Primary HLH which occurs due to genetic defects often requires hematopoietic stem cell transplant for permanent restoration of normal immune function.
| Conclusion|| |
We present an unusual case of HD presenting with HLH and cerebellar signs. Pathophysiology of both these entities is still obscure. HLH can have a nonspecific presentation and requires a high index of clinical suspicion for diagnosis. Comprehensive testing and accurate diagnosis are important strategies for successful treatment of patients with HLH. Early treatment with chemotherapy usually rectifies the HLH and neurological symptoms associated with HL.
Written informed consent was obtained from the patient. The patient has given her consent for her images and other clinical information to be reported in the journal.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initial will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mustafa Ali M, Ruano Mendez AL, Carraway HE. Hemophagocytic Lymphohistiocytosis in a Patient with Hodgkin lymphoma and Concurrent EBV, CMV, and Candida Infections. J Investig Med High Impact Case Rep 2017;5:2324709616684514.
Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al.
HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-31.
Knox B, Singh D, Mai H, Mirza K. Hodgkin's lymphoma with HLH and complete remission with brentuximab-based therapy. BMJ Case Rep 2019;12:e231629.
Rouphael NG, Talati NJ, Vaughan C, Cunningham K, Moreira R, Gould C. Infections associated with haemophagocytic syndrome. Lancet Infect Dis 2007;7:814-22.
Hyun G, Robbins KJ, Wilgus N, Grosso L, Goyal SD: Hemophagocytic lymphohistiocytosis in a patient with classical Hodgkin lymphoma. Case Rep Hematol. 2016, 2016:2103612.
Grimm S, Chamberlain M. Hodgkin's Lymphoma: A Review of Neurologic Complications. Adv Hematol. 2011;2011:624578.
Song Y, Pei RJ, Wang YN, Zhang J, Wang Z. Central nervous system involvement in hemophagocytic lymphohistiocytosis in adults: A retrospective analysis of 96 patients in a single center. Chin Med J (Engl) 2018;131:776-83.
Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood 2011;118:4041-52.
[Figure 1], [Figure 2], [Figure 3]