Abstract
Introduction
Primary central nervous system (CNS) involvement of Hodgkin's lymphoma is very uncommon. There are only a few previous reports of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS concurrently with systemic disease.
Case presentation
A 12-year-old boy with a history of painless left inguinal swelling and acute diplopia. There was an intensely enhancing lesion in the right midbrain on magnetic resonance imaging. The patient was diagnosed with stage IV Hodgkin's lymphoma of nodular lymphocyte predominance type by routine microscopy and immunohistochemistry of left inguinal lymph node biopsy with computed tomography-assisted staging. It was planned to treat him with six cycles of chemotherapy with intrathecal methotrexate, followed by radiotherapy to the CNS lesions. After two cycles of chemotherapy, the patient entered complete remission of all lesions including the CNS lesion documented by the positron emission tomography scan.
Conclusion
We are describing the course of this rare presentation of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS and clinical challenge in its diagnosis and management of this case.
Background
Hodgkin's lymphoma (HL) most commonly presents with progressive, painless enlargement of peripheral lymph nodes, especially around the cervical region or less frequently mediastinal or abdominal lymph nodes and progresses to other groups of lymph nodes and eventually to non-lymphoid organs. HL involves the central nervous system (CNS) in 0.2–0.5% of cases either by contiguous or hematogenous spread.Citation1,Citation2
CNS involvement is more common in patients with widespread relapsed disease or at initial diagnosis in immunocompromised patients, but can also be seen at initial diagnosis in immunocompetent patients.Citation3 HL presenting as a lesion of the brain stem is less common than other intracranial sites.Citation1,Citation4–Citation7 Mixed cellularity histology is the most frequent subtype of Hodgkin's disease among these patients, but our patient has presented with HL with nodular lymphocyte predominance.Citation8,Citation9 Epstein–Barr virus (EBV)-associated polymorphic lymphoproliferative disorders (PLDs) can resemble more like HL. PLDs in which the atypical cells almost universally express B-cell markers and carry EBV genome.Citation10 Although this is an uncommon clinical scenario, healthcare professionals should be aware of this possibility of HL with nodular lymphocyte predominance involving the midbrain.
Case presentation
A 12-year-old boy presented with a history of painless left inguinal swelling of 1-month duration and abrupt onset of disabling diplopia without B symptoms. Physical examination revealed an enlarged left inguinal lymphadenopathy, bilateral tonsillar enlargement, paralysis of lateral gaze on the left eye, and nystagmus with right lateral gaze.
Laboratory examinations revealed normal complete blood count and biochemical parameters. The patient underwent computed tomography (CT)-assisted staging, neuroaxis magnetic resonance imaging (MRI), lumbar puncture, and bone marrow biopsy. These studies demonstrated prevascular, pretracheal, and supraclavicular lymphadenopathy; intensely enhancing lesion in the right midbrain (measuring 16 × 17 mm, A–C); normal cerebrospinal fluid (CSF) protein and negative CSF cytology; and negative bone marrow pathology. Serologic testing for HIV, EBV, and hepatitis B and C virus was negative. On positron emission tomography (PET) scan showed increased fludeoxyglucose (FDG) uptake in the left external iliac and inguinal lymph node regions (largest measuring 2.0 × 1.5 cm, standardized uptake value (SUV)-6), bilateral level II cervical lymph nodes (largest measuring 2.2 × 0.9 cm, SUV-2.7), adenoids and bilateral palatine tonsils (SUV-8.53), and three nodular enhancing lesions (SUV-8.5) in the right thalamus (1.1 × 0.7) and midbrain (1.3 × 1.0 and 0.6 × 0.4 cm) with perilesional edema and mass effect. Pathologic evaluation of left inguinal lymph node biopsy demonstrated a fibrous tumor composed of small lymphocytes and scattered plasma cells consistent with nodular lymphocyte predominance type of HL (). The lymphocytic and histiocytic cells express LCA, Pax-5, CD20, and OCT 1, and are immunonegative for CD30, CD15, and CD3. He underwent tonsillectomy as there was bilateral tonsillar enlargement and histopathological examination revealed reactive tonsillar lymphoid tissue. In view of the difficulty in obtaining tissue from the brain stem lesion without long-term neurological morbidity, the brain stem lesions were presumed to be involved and treated with intravenous steroids and intrathecal methotrexate with resolution of diplopia.
Figure 1. Pre-treatment magnetic resonance imaging with coronal (A) and sagittal T2 (B) with contrast (C) images showing intensely enhancing lesion in the right midbrain.
Figure 2. HPE (hematoxylin and eosin stain (H&E)) of right inguinal lymph node biopsy showing microscopic sections: a predominant nodular pattern (A) with morphologically typical Reed-Sternberg cells, the popcorn cells (B) showing positive immunostaining with CD45 (D), CD20 (C), OCT (E) positivity with CD30 negativity and (F) CD 30 negativity is not present.
The patient's stage IV HL is planned to be treated with six cycles of chemotherapy with cyclophosphamide, vincristine, prednisolone, procarbazine, doxorubicin, bleomycin, and vinblastine (COPP/ABV), with 6 monthly treatments of intrathecal methotrexate on day one of each cycle, followed by radiotherapy to the CNS lesions. After two cycles of COPP/ABV, the patient entered complete remission of all lesions including the CNS lesion as documented by the MRI (A–C) and PET CT scan. PET CT scan after six cycles of chemotherapy has shown complete resolution of all previously seen CNS lesions without any metabolic activity (). The patient was treated with external radiation on 6 mv LINAC to a dose of 23.4 Gy to the whole brain followed by 6 Gy to the pre-chemotherapy tumor volume with 5 mm margins. Overall treatment was well tolerated by the patient without treatment breaks. The patient is currently on 2 monthly outpatient follow-up.
Figure 3. Post-treatment magnetic resonance imaging with coronal (A) and sagittal T2 (B) with contrast (C) showing intensely enhancing lesion in the right midbrain.
Figure 4. Pre-treatment and post-treatment positron emission tomography computed tomographic scan images of midbrain lesion suggestive of remission of disease.
Conclusion
Etiology, treatment, and prognosis of intracranial HL have not been established.Citation11 Common presentations include cranial nerve palsies, motor and/or sensory deficits, headaches, papilledema, coma, and seizures.Citation8 The most common presenting feature of intracranial Hodgkin's disease is cranial nerve palsy.Citation12 Brain parenchymal involvement shows a predilection for supratentorial lesions, this being the most common intracranial site of involvement.Citation1,Citation4–Citation7,Citation12,Citation13 Mixed cellularity histology is the most frequent subtype of Hodgkin's disease among these patients,Citation8,Citation9,Citation12,Citation13 although the case reported by Vetter et al.Citation14 was of nodular lymphocyte predominance. The distinction between HL and HL-like PLD is often challenging and perhaps arbitrary. Atypical cells in such PLD cases usually are B cells expressing CD20, CD30, CD45, and EBV antigens, the latent membrane protein (LMP-1), and/or the Epstein–Barr virus-encoded RNA 1 (EBER-1). In our patients, diagnosis of nodular lymphocyte predominant HL was confirmed by the absence of CD30 and EBV-associated antigens on immunohistochemistry.Citation10 Median survival following local (10–20 Gy) and whole-brain (30–40 Gy) radiotherapy has been reported in the range of 8 months to 2 years.Citation4 Systemic chemotherapy in combination with radiotherapy has been advocated, and treatment protocols have included ABVD, COPP (cyclophosphamide, vincristine, procarbazine, prednisone), MOPP (nitrogen mustard, vincristine, procarbazine, prednisone), and/or intrathecal methotrexate.Citation2,Citation3,Citation6,Citation11 Long-term disease-free survival has been reported following combined-modality therapy.Citation2,Citation3,Citation6,Citation8
In this case report, the patient was diagnosed with stage IV nodular predominance Hodgkin's lymphoma (NPLHL) on histopathology and immunohistochemistry of the left inguinal lymph node. We had faced clinical dilemma in conducting a diagnostic biopsy from the brain stem (view of proximity to vital centers) and decision regarding appropriate combination chemotherapy with adequate CNS activity. Despite need for histopathological evidence, we proceed to systemic combination chemotherapy COPP/ABV protocol without biopsy. Use of alkylator-based therapy may have an advantage over non-alkylator-based regimens in NLPHL. This is supported by various retrospective studies and so we initiated COPP/ABV protocol with intrathecal methotrexate.Citation15–Citation19 Thus, we present the case report of an unusual intracranial site of NPLHL in the brain stem and clinical challenge in its diagnosis and management of this case.
Disclaimer statements
Contributors All authors have revised the manuscript critically and gave final approval of the version to be published.
Funding None.
Conflicts of interest None.
Ethics approval Written informed consent was obtained from the subject for publishing this case report and accompanying images.
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