Classical Nodular Sclerosis Hodgkin lymphoma presenting with central nervous system disease.

To the Editor: The incidence of primary classical nodular sclerosis (CNS) lymphoma has increased significantly over the last 2 decades. Non-Hodgkin lymphomas (NHL) of B-cell origin account for the majority of these neoplasms. In contrast to NHL, CNS involvement by Hodgkin lymphoma (HL) is exceedingly rare. In a large clinical series of 2185 patients of HL, CNS involvement was seen in only 0.2% cases. (1) All of these cases with CNS involvement were seen at relapse, along with disseminated systemic disease. Presentation of HL with a primary intracranial lesion is extremely rare, with only sporadic cases reported in the literature. We report the following case of biopsy proven Classical Nodular Sclerosis Hodgkin lymphoma presenting in a young male with simultaneous intracranial and spinal involvement, along with nodal disease.

A 38-year-old male presented with vertigo to our ENT outpatient clinic. MRI of the brain showed a contrast enhancing lesion located at the roof of the fourth ventricle extending into the pons with significant edema. He was then lost to follow-up and again presented a month later with diplopia. Repeat MRI showed the same pons lesion with increased surrounding edema and mass effect along with a prominent enhancing lesion along the left aspect of the cauda equina. CT scan of chest abdomen and pelvis showed enlarged retroperitoneal nodal masses. Given his progressing neurologic symptoms, he was started immediately on radiotherapy (XRT) and parentral steroids, which resulted in significant symptomatic improvement. At this point, with a high clinical suspicion for primary CNS NHL, an Ommaya reservoir was placed and the patient was given intrathecal and systemic methotrexate. Cytology from the CSF was negative for malignant cells on multiple occasions. After 2 nondiagnostic CT guided biopsies, a laparoscopic biopsy of the retroperitoneal lymph nodes demonstrated, to our surprise, classical Nodular Sclerosis HL. There was extensive architectural effacement by a diffuse and vaguely nodular proliferation with birefringent collagen bands around some nodules, a sclerotic nodal capsule and some diffuse sclerosis. There were predominantly small lymphocytes with a moderate number of scattered large cells, many of which had prominent nucleoli, some of which were binucleate and some of which were in lacunar spaces. Immunohistochemical stains showed that the large atypical cells were positive for CD15 and CD30, mostly negative for CD20 and Oct 2, and negative for CD79a, CD45, Bob. (1), MUM-1, PAXS (weak) and T-cell associated antigens. No clonal T-cell receptor (TCR) gamma chain gene rearrangement was detected by PCR. A definitive diagnosis of classical Nodular Sclerosis HL was therefore rendered. The lesions in pons and cauda equina were not biopsied due to the high risks involved in biopsying the brainstem and the visible clinical improvement on current therapy. The patient was discharged for XRT followed by chemotherapy on the Stanford V protocol as an outpatient. He showed steady improvement through the course of radiation. At the end of treatment, his cranial nerve deficits had resolved completely, and repeat imaging showed complete resolution of the CNS disease and retroperitoneal lymphadenopathy. At one year follow-up, he remained in remission.

Presentation of Hodgkin lymphoma with CNS involvement is extremely rare, with only 11 such prior case reports found in a literature search. (2-5) The most common form of involvement was a dural-based parenchymal mass. Posterior fossa/brainstem involvement was seen in only 36% of the cases, all of which had a cerebellar lesion. None of the cases had pontine involvement. The most common histologic type of HL among these cases was nodular sclerosis. Treatment modalities used were neurosurgery, intrathecal chemotherapy, systemic chemotherapy and radiotherapy. Chemotherapy protocols used included ABVD, MOPP and CHOP. Regardless of the treatment modalities used, complete remission was achieved in all cases, along with resolution of neurologic manifestations. No uniform risk factors for neurologic involvement by Hodgkin lymphoma have been identified so far.

Akshay K. Gupta, MD

Department of Medicine

University of Pittsburgh Medical Center 

Dennis Meisner, MD

Division of Hematology and Oncology

Department of Medicine

Hillman Cancer Center

University of Pittsburgh Medical Center

Neetu Talreja

Department of Medicine

Western Pennsylvania Hospital

Temple University School of Medicine 

Ryan Smith, MD

Department of Radiation Oncology

University of Pittsburgh Medical Center

Steven H. Swerdlow, MD

Department of Pathology

Division of Hematopathology

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania

References

1. Sheehan T, Cuthbert RJ, Parker AC. Central nervous system involvement in haematological malignancies. Clin Lab Haematol 1989;11:331-338.

2. Bender BL, Mayernik DG. Hodgkin disease presenting with isolated craniospinal involvement. Cancer 1986;58:1745-1748.

3. Deckert-Schluter M, Marek J, Setlik M, et al. Primary manifestation of Hodgkin disease in the central nervous system. Virchows Arch 1998;432:477-481.

4. Figueroa BE, Brown JR, Nascimento A, et al. Unusual sites of Hodgkin lymphoma: CASE 2: Hodgkin lymphoma of the CNS masquerading as meningioma. J Clin Oncol 2004;22:4228-4230.

5. Hirmiz K, Foyle A, Wilke D, et al. Intracranial presentation of systemic Hodgkin disease. Leuk Lymphoma 2004;45:1667-1671.

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