Brain Pathology Case of the Month - August 2018

FINAL DIAGNOSIS

Chordoid meningioma with Castleman Syndrome.

DISCUSSION

The diagnosis of the present case was Castleman syndrome caused by chordoid meningioma, combined with cervical cord lesion and visual disturbance. Castleman disease (CD) is a rare lymphoproliferative disease, generally presents with clinical findings such as fever, anemia, hypergammaglobulinemia, and an increased plasma level of acute phase proteins. Those clinical abnormalities usually disappear after resection of the affected lymph nodes, and chemical mediators such as IL-6 released from the lymph nodes are believed to cause inflammatory reactions.

Castleman syndrome (CS) has been reported to cause various clinical symptoms similar to those of CD without lymphoproliferation. Since the first case of CS due to intracranial meningioma was documented in 1980, 15 CS cases involved with meningioma have been reported. Most of these tumors were chordoid meningiomas characterized by a histological finding of chordoma-like appearance with lymphoplasma cell infiltration, whereas other types of meningioma are rarely associated with CS. Although most cases of CS demonstrate elevated level of serum IL-6, the precise mechanism of IL-6 production by meningioma is unclear.

In our case, the level of serum IL-6 significantly decreased following the removal of the chordoid meningioma, and the clinical abnormalities such as anemia, weight loss, fever, and other inflammatory reactions, also resolved. These clinical improvements after surgical resection of the tumor are frequently observed in CS, implying that IL-6 might largely attribute to the clinical manifestations of CS.

Although many tumors are known to release IL-6, the production of IL-6 by meningioma has been scarcely reported. Arima et al. demonstrated the upregulation of IL-6 in the histologically diagnosed 'chordoid meningioma' cells by RT-PCR using fresh-frozen sections [1]. Denaro et al. performed immunohistological analyses, the chordoid meningioma specimens were tested for the expression of various antibodies [3]. They revealed that the tumor was focally positive for IL-6 but not for TNFa. Recently, we also reported the overexpression of IL-6 in the cerebrospinal fluid (CSF) of primary central nervous system lymphoma patients [4]. Although the autocrine IL-6 signaling is suggested to play a critical role in STAT3-dependent tumor progression [2], further investigation is necessary to clarify the molecular activity of IL-6 produced by meningiomas.

Moreover, in our case, the patient manifested left hemiparesis/hypesthesia and visual impairment. To the best of our knowledge, no case of CS with such neurological deficits has been mentioned in the literature. All the positive results of various clinical examinations were CSF oligoclonal band (OCB) testing and immunohistochemistry for the antibody against normal optic nerve fiber in the patient's preoperative serum. Because left hemiparesis/hypesthesia had improved after surgical resection of the chordoid meningioma and has not relapsed in the postoperative course and oligoclonal band and high IgG index in the CSF were observed, we considered the coexisting demyelinating disease of the cervical cord, but a definitive diagnosis could not be established. There is no report of demyelinating disease associated with Castleman syndrome (or disease), although Castleman disease -associated peripheral neuropathy is reported. On the other hand, for the visual disturbance, we considered 'paraneoplastic optic neuropathy (PON)', 'neuromyelitis optica (NMO)' or 'multiple sclerosis' as differential diagnoses. According to the result of anti-aquaporin 4 antibody in CSF and immunoreactivity of the patient`s serum with rat, monkey, and human optic nerve sections, some autoimmune mechanisms were suspected to contribute to the disorder, we finally considered this case as PON.

REFERENCES

  1. Arima T, Natsume A, Hatano H, Nakahara N, Fujita M, Ishii D, et al, (2005) Intraventricular chordoid meningioma presenting with Castleman disease due to overproduction of interleukin-6. Case report. J Neurosurg 102:733-737
  2. Chang Q, Bournazou E, Sansone P, Berishaj M, Gao SP, Daly L, et al, (2013) The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. Neoplasia 15:848-862.
  3. Denaro L, Di Rocco F, Gessi M, Lauriola L, Lauretti L, Pallini R, et al, (2005) Pyrogenic cytokine interleukin-6 expression by a chordoid meningioma in an adult with a systemic inflammatory syndrome. Case report and review of the literature. J Neurosurg 103:555-558
  4. Sasayama T, Nakamizo S, Nishihara M, Kawamura A, Tanaka H, Mizukawa K, et al, (2012) Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL). Neuro Oncol 14:368-380.

Contributed by Hirotomo Tanaka, Daisuke Yamamoto, Katsu Mizukawa, Akiyasu Kanamori, Norio Chihara, Ryosuke Matsuoka, Shigeo Hara, Takanori Hirose, Takashi Sasayama, Eiji Kohmura

International Society of Neuropathology