Brain Involvement In Hodjkins Disease

CASE REPORT

CASE

REPORT

Radiation Medicine: Vol. 18 No. 3, 205–208 p.p., 2000

Brain Involvement in Hodgkin’s Disease: Case Reports and Review of the Literature Hidetsugu Nakayama,*,# Koichi Tokuuye,* Yoshikazu Kagami,* Minako Sumi,* Sigeyuki Murayama,* Mitushiko Kawashima,* Atsushi Imai,* Hiroshi Ikeda,* and Kensei Tobinai** Hodgkin’s disease involving in the central nervous system is extremely rare.1 It usually spreads contiguously, 2 as visceral involvement is generally thought to occur secondary to involved adjacent lymph nodes. We report three such cases found in our institution in the last two decades. Based upon our limited experience together with reported data, whole brain irradiation combined with systemic chemotherapy remains the treatment of choice for these lesions. Key words: brain involvement, Hodgkin’s disease CASE REPORTS Case 1 A 17-year-old man was admitted to the National Cancer Center Hospital, Tokyo, in September 1985, with an anterior chest wall mass extending to the mediastinum and, swollen supraclavicular and cervical lymph nodes associated with a high fever of three month’s duration. Histological examination of the cervical lymph node revealed Hodgkin’s disease (HD) of the nodular sclerosis type. Abdominal and pelvic computed tomography (CT) and bone marrow aspiration biopsy were negative for tumor involvement; thus, the patient was classified as having a clinical stage IIB disease. He first underwent three courses of chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) followed by radiotherapy to the mantle field, receiving 39 Gy in 22 sessions, which resulted in only partial response. In May 1986, he received two additional courses of chemotherapy with ABVD, but in September 1986 relapse occurred in the second to sixth thoracic Received September 22, 1999, revision accepted January 17, 2000. * Radiation Oncology Division, National Cancer Center Hospital ** Medical Oncology Division, National Cancer Center Hospital # Present affiliation: Radiation Oncology Division, Ibaraki Cancer Center Hospital (Tsukuba Medical Center Hospital) Financial support: Grant-in Aid for Cancer Research (9-43) from the Ministry of Health and Welfare of the Japanese Government Reprint requests to Hidetsugu Nakayama, M.D., Radiation Oncology Division, Ibaraki Cancer Center Hospital (Tsukuba Medical Center Hospital), 1-3-1 Amakubo, Tsukuba, Ibaraki 3058558, JAPAN. Volume 18, Number 3

vertebrae, the third rib, postauricular lymph node, Waldyer’s ring, and mediastinal mass. These lesions were treated with 19 repeated courses of various chemotherapies and two courses of radiotherapy. In September 1994, he complained of gait disturbance, memory loss, and upper arm weakness. Cranial CT examination disclosed a 3-cm-sized solitary brain tumor in the corups callosum. He underwent whole brain radiotherapy of 35 Gy in 14 sessions, and the tumor disappeared one month later. In April 1996, he experienced the same symptoms, including upper arm weakness and memory loss, and cranial CT revealed recurrence at the same site (Fig. 1a). This lesion was treated with fractionated stereotactic radiotherapy3 of 44 Gy in 11 fractions. The tumor remained under control for 24 months after treatment (Fig. 1b), however cerebellar metastases appeared 14 months later. In March 1998, he died of progressive HD. Case 2 A 31-year-old woman was admitted in January 1981 with cervical lymph node swelling. Chest and abdominal CT and gallium scintigraphy disclosed an anterior mediastinal mass. Histological examination of the mass revealed HD of the lymphocyte depletion type. After negative bone marrow aspiration biopsy for hematological extension, she was diagnosed as having clinical stage IIA disease. She underwent six courses of chemotherapy with C-MOPP (cyclophosphamide, vincristine, procarbazine, and prednisolone). In May 1982, she developed submandibular lymph node swelling, which was treated with radiotherapy of 40 Gy in 20 sessions. In November 1983, she received 37.5 205

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Fig. 1. Gd enhancement reappeared in the same area 8 months after whole brain irradiation. The tumor was well controlled using fractionated stereotactic radiotherapy. a The figures show MRI images taken before (a) and 1 year (b) after treatment.

Gy in 25 sessions to the enlarged abdominal paraaortic lymph nodes through an inverted Y field. In May 1986, she had right hemi-sided convulsion with an increased bilateral tendon reflex, and cranial CT examinations revealed a left parietal solitary mass. She underwent whole brain radiotherapy, receiving 40 Gy in 20 sessions, and the tumor disappeared two months later. In February 1990, she suffered from multiple relapses including the mediastinum, left femoral bone, and inguinal, pelvic and paraaortic lymph nodes. She was successfully treated with repeated radiotherapy alone because she refused further chemotherapy. In July 1990, she died of pneumonia. Case 3 A 42-year-old woman suffered from left cervical lymphadenopathy and was diagnosed in September 1971 to have Hodgkin’s disease, mixed cellularity type, clinical stage IIB. Although she underwent cyclophsphamide and vinblastine chemotherapy, residual tumors remained. In March 1976, she underwent CHOP chemotherapy (cyclophsphamide, doxorubicin, vincristine, and prednisone) for continual fever and hepatomegaly, a sign of HD involvement; however, the symptoms did not improve. In September 1976, she was referred to the National Cancer Center Hospital, with high fever and left cervical lymphoadenopathy. She received additional chemotherapy using various drugs for the mediastinal relapses and abdominal and pelvic lymph node swelling. In January 1985, she developed akinesis, and cranial CT examinations revealed a hypothalamic mass. She underwent whole brain radiotherapy, but this was discontinued because she 206

b

developed pneumonia, of which she died in April 1985. DISCUSSION Brain involvement in HD is rare: only 25 reports involving 48 patients were published during the period from 1954 to 1999. 1,2,4-29 The mechanism of brain involvement is through either direct tumor extension through the skull bone or meningeal involvement,4,8,11 or systemic hematogenous dissemination rather than contiguous local invasion.2,5,17 In our cases, all brain lesions were solitary and deeply seated, suggesting hematogenous spread. In our cases, the diagnosis for HD brain involvement was based on the symptoms and radiological findings (Table 1). Brain involvement occurred late, 4-14 years after evidence of systemic involvement. Lesion response after whole brain irradiation was noted in 2 to 3 months but may be temporary. Among the 48 patients reported in the literature, the varieties of subhistology were comparable with the reported natural distributions of HD subhistology. The median age was 31.9 years, ranging from 11 to 69 years, with an equal male/female ratio. Treatment strategies for brain involvement include whole brain irradiation and systemic chemotherapy. Among age, histology, stage, and initial treatment method, the most significant prognostic factor in the 48 cases appeared to be whole brain irradiation. The combination of radiotherapy and chemotherapy seemed to prolong survival rates and the interval between initial diagnosis and brain involvement. Sapozink et al. recommended a radiation dose of 30 Gy covering the RADIATION MEDICINE

CASE REPORT Table 1. Patients with intracranial Hodgkin’s disease treated at National Cancer Center (1972-1999) Interval (month) Patient

Age

Sex

Initial stage

Histology

1 2 3

17 31 42

M W W

IIB IIA IIB

NS LD MC

Diagnosis to intracranial presentation 115 47 168

Survival (month) Neurologic symptoms

From diagnosis

From intracranial presentation

Gait disturbance Convulsion Akinesis

146 97 170

31 50 2

NS: nodular sclerosis, LD: lymphocyte depletion, MC: mixed cellularity

whole brain and an additional 10 to 20 Gy to the involved area plus systemic chemotherapy.1 Komatsu reported a patient with brain metastases who had survived more than 2 years following whole brain radiotherapy plus systemic chemotherapy, and recommended a combination of radiotherapy and chemotherapy.26 Therefore, whole brain irradiation and systemic chemotherapy remain the treatment of choice for brain involvement in patients with HD. ACKNOWLEDGMENT This study was supported in part by a Grant-in-Aid for Cancer Research (9-43) from the Ministry of Health and Welfare of the Japanese Government.

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9) Gaelon LH, Levitan S. Solitary intracranial metastasis by Hodgkin’s disease. Arch Intern Med, 120: 740–745, 1967. 10) Sohn D, Valensi Q, Miller SP. Neurological manifestations of Hodgkin’s disease: Intracerebral Hodgkin’s granuloma. Arch Neurol, 17: 429–436, 1967. 11) Buckley TF, Warwick F. Surgical management of intracranial Hodgkin’s disease. J Neurol Neurosurg Psychiat, 31: 612–615, 1968. 12) Currie S, Jardine GWH. Intracranial Hodgkin’s disease shown by radioisotope scan. J Neurol Neurosurg Psychiat, 32: 313–316, 1969. 13) Thompson RW, Denardo GL. Therapeutic response of intracranial Hodgkin’s disease documented by brain scanning, Cancer, 24: 981–984, 1969. 14) Reagna TJ, Derby BM. Intracerebral Hodgkin’s disease. Dis Nerv Sys, 32: 843–847, 1971. 15) Biran S, Herishianu Y. Brain involvement in Hodgkin’s disease: Report of a case. Eur Neurol, 8: 352–358, 1972. 16) Branzinsky JH. Metastatic intracerebral and intracerebellar Hodgkin’s disease. J Neurol, 38: 635–637, 1973. 17) Scheithauer BW. Cerebral metastasis in Hodgkin’s disease. Arch Pathol Lab Med, 103: 284–287, 1979. 18) Cuttner J, Meyer R, Huang YP. Intracerebral involvement in Hodgkin’s disease: A report of 6 cases and review of the literature. Cancer, 43: 1497–1506, 1979. 19) Alvarez F, Road JM, Ancines B, Alvarez MP. Intracranial Hodgkin’s disease. J Neurosurg Sci, 29: 273–277, 1985. 20) Blake PR, Carr DH, Goolden AWG. Intracranial Hodgkin’s disease. Br J Radiol, 59: 414–416, 1986. 21) Ashby MA, Bowen D, Watson JV. Intracranial Hodgkin’s disease: a primary presentation and access of cytotoxic agents. Br J Radiol, 59: 1241–1242, 1986. 22) Scully RE, Mark EJ, Mcneely WF, Mcneely BU. Case records of the Massachusetts General Hospital. New Engl J Med, 320: 447–457, 1989. 23) Iwata Y, Akiguchi I, Ogawa H, et al. Hodgkin’s disease with involvement of the brain. Report of a case. J Jpn Soc Intern Med, 66: 837–844, 1977. (in Jpse.) 24) Onozawa Y, Yahara Y, Yoshida M, Handa T, Kamiyama R. A case report of brain invasion of Hodgkin’s disease. Jpn J Clin Haem, 27: 1076–1079, 1986. (in Jpse.) 25) Hasegawa M, Nakajima K, Mori M, Tanimoto K, Suzuki 207

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