Primary epidural lymphocyte-depleted Hodgkin’s lymphoma of the thoracic spine – presentation of a rare disease variant
© Kasper et al.; licensee BioMed Central Ltd. 2012
Received: 29 March 2012
Accepted: 19 July 2012
Published: 3 August 2012
Lymphocyte-depleted Hodgkin’s lymphoma is the rarest form of classical Hodgkin’s lymphoma, accounting for < 1% of all cases. Patients often have advanced-stage disease at the time of presentation with an aggressive clinical course. Even more uncommon is primary extranodal disease and rarely it will be presenting with spinal cord compression.
An 88-year-old Caucasian female presented with a history of upper back pain for several months and new onset bilateral leg numbness and weakness. MRI of the spine showed a dorsal epidural lesion with cord compression at T1-T4 with involvement of the paraspinal muscles. The patient received urgent surgical decompression, with final histopathology showing a lymphocyte-depleted Hodgkin’s lymphoma. Systemic work-up did not show evidence of nodal disease. Following surgery, she received a course of radiotherapy with good outcome.
To the best of our knowledge, this is the first reported case of primary lymphocyte-depleted Hodgkin lymphoma presenting as epidural spinal cord compression. Our report, in conjunction with a review of the literature, suggests that surgical intervention is clearly indicated in de novo disease followed by radiotherapy.
KeywordsSpinal cord compression Primary Lymphocyte-depleted Hodgkin’s lymphoma
Hodgkin’s lymphoma (HL) usually presents with painless enlargement of peripheral lymph nodes, mostly in the cervical region in 90% of cases, with only 10% arising from extranodal regions . Approximately 5-20% of patients with HL develop osseous involvement during the course of their disease [2–6], but only 0.25% present in a primary fashion .
Evidentiary table of case reports of primary epidural spinal Hodgkin’s lymphomas
Levels of Disease
Al-Khayat H et al, 2007
47 yo female
Bilateral hand weakness
Cagavi F et al, 2006
30 yo male
Low back pain
Citow JS et al, 2001
54 yo female
Upper back pain
Higgins SA et al, 1995
46 yo female
Lower extremity numbness
Illes A et al, 2002
32 yo male
Patients usually present with back pain and/or neurologic deficits specific to the level of the lesion, along with lymphoma-related B-type symptoms of weight loss, night sweats, and fever. Tumors have a preference for the dorsal aspect of the thoracic spine, followed by lumbar and cervical regions, likely due to the rich venous anatomy in the thoracic region [8, 16, 17]. The absence of bony involvement limits the usefulness of plain films. PESL appears isointense on T1-weighted images and is iso- to hyperintense on T2-weighted MRI with marked contrast enhancement [17, 18]. MRI can clearly delineate the tumor as well as the involvement of the surrounding tissues. To complete the diagnostic workup of PESL, one should also include a contrast MRI of the entire neuraxis, body CT scan, bone marrow biopsy, bone scan, and CSF analysis [9, 19].
Lymphocyte-depleted Hodgkin’s lymphoma (LDHL) is rarest subtype of classic Hodgkin’s lymphoma (CHL), initially recognized in 1966 , and comprising approximately < 1% of all cases of CHL . Morphologically, these tumors can mimick other anaplastic malignancies including non-Hodgkin’s lymphomas, nodular sclerosis Hodgkin’s lymphoma with lymphocyte depletion, carcinoma, sarcoma, and melanoma . Many earlier cases of LDHL have since been reclassified as anaplastic variants of diffuse large B-cell lymphoma or anaplastic large cell lymphoma . LDHL has a male predominance (60-75% of cases) with an median age range of 30-37 years [23, 24] with a predilection for nodes in the retroperitoneum, abdomen, thorax, and abdomen, with relative sparing of the peripheral lymph nodes [21, 25]. A recent study has found an association between LDHL and HIV-positive status .
Immunohistochemical markers for Lymphocyte-depleted Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma
PAX5 (weak), CD30, CD15, MUM-1, fascsin, Oct.2 or Bob-1 (not co- expressed)
PAX5 (strong), CD20, CD79a (B cell NHL), EMA, ALK-1, Oct.2 and Bob-1 (always co-expressed)
Goals of treatment echo those of any lesion causing epidural spinal cord compression: decompression of the neural elements, tissue diagnosis, and spinal stabilization . In cases of primary disease presenting with spinal cord compression, surgical debulking is mandated and also allows for adequate tissue sampling for diagnosis . This is followed by radiation therapy alone or in conjunction with chemotherapy but rarely with chemotherapy alone [19, 28, 29]. Rathmell et al reported a 33% actuarial survival rate in patients treated with radiation alone compared to 86% with combination therapy , while Monnard et al found that combined treatment was statistically superior to radiotherapy alone . This is similar to treatment for NHL, although therapy for NHL varies according to the histological type and disease grading, with chemotherapy alone for nonindolent variants, while radiotherapy alone is used in indolent stage I and contiguous stage II NHL. This is in contrast to emerging treatment of indolent noncontiguous stage II, III, and IV NHL with antibodies directed to presenting B-cell antigens in combination with systemic chemotherapy. Aggressive NHL is treated using a combination of chemotherapy and involved-field radiation therapy, which has shown to be more effective than just chemotherapy alone. To the best of our knowledge, there have been no previous reports of a primary epidural spinal LDHL causing spinal cord compression. We herein report our findings to highlight this extremely rare subtype of CHL and also to emphasize the importance of diligent investigation in a patient that presents with back pain and unremarkable plain film xrays.
An 88 year-old Caucasian female was seen by the neurosurgical service with worsening pain between her scapula and difficulties ambulating. She had had upper back pain for several months. She underwent work up with plain films which did not show any abnormalities, and had been managed conservatively by pain management clinics. Over the past 4 weeks, she had developed progressive lower extremity weakness, requiring a walker for ambulation. She was admitted to hospital for medical management of her back pain and over the course of the next 48 hours, she had subjective worsening of her lower limb weakness. A review of systems was negative for malignancy or B-type symptoms.
Physical examination was negative for lymphadenopathy. Neurologic examination was significant for a positive Rhomberg’s sign and decreased pinprick sensation in both legs extending to the hip (approximately to the L2 distribution). She had loss of proprioception in all extremities. Rectal tone was normal. Toe responses were described as extensor on the left and equivocal on the right. Blood panel showed normal values apart from slight anaemia and mildly elevated platelets.
The patient was taken urgently to the operating room for a decompressive laminectomy from T1-T4. The epidural mass was diligently resected to decompress the cord. Frozen tissue histology confirmed a malignant infiltrative tumor initially suggestive of a carcinoma, which prompted us to also excise the surrounding involved paraspinal tissues. Given her advanced age, extensive tumor burden, and preexisting comorbidities, we opted for a wide decompression of the spinal cord but no further aggressive surgical measures.
Following surgery, she had persistent loss of proprioception with an unsteady gait, which we attributed secondary to prolonged compression of the dorsal columns by the circumferential tumor mass. She demonstrated myelopathic symptoms with mild hyperreflexia to her lower extremities and Babinski reflexes on postoperative exam (which were present prior to surgical decompression). Systemic workup, including a PET study, did not show nodal disease or presence of extranodal involvement outside of the symptomatic thoracic region. CSF was not examined due to the primary epidural nature of the disease. Combination therapy was offered to the patient, but after extensive counseling, she opted for radiotherapy alone, not wanting to experience the possibly significant side-effects of chemotherapy and the resultant need for prolonged hospital stay to receive treatment. She thus received ten treatments of external beam radiation at 3 Gy fractions for a total of 30 Gy, from which she was experiencing mild fatigue, esophagitis, and moderate erythema to the treatment area. At the end of therapy, she had 5/5 strength in the upper and regained 4/5 strength in the lower extremities on exam. She was transferred to a palliative care unit where she lived well until she died of cardiopulmonary complications at 5 months.
Bone involvement is common during the course of both Hodgkin’s and non-Hodgkin’s lymphoma, but rarely presents with epidural spinal cord compression. The initial manifestation of such lymphoproliferative disorders in the spine is a very rare entity and even more so when encountered as an isolated disease focus, hence its place on the list of differential diagnosis in patients who present with back pain and compressive myelopathy are unfamiliar to most clinicians. The clinical, radiological, and histological features of this disease can mimic other medical conditions leading to canal compromise, including pathological compression fractures, infectious lesions (such as tuberculosis and osteomyelitis), or carcinomatous deposits. This makes the correct diagnosis difficult and often leads to significant delays until effective treatment is initiated.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Classic Hodgkin’s lymphoma
Lymphocyte-depleted Hodgkin’s lymphoma
Primary epidural spinal lymphoma RS = Reed-Sternberg.
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