Neuromyelitis optica spectrum disorder and adenocarcinoma of ovary: a novel association

Abstract

Paraneoplastic neuromyelitis optica spectrum disorder (NMOSD) is a rare clinical entity with less than 40 cases described in literature until today. Paraneoplastic NMOSD in association with adenocarcinoma of ovary has not been described yet. We present a case of paraneoplastic NMOSD in association with carcinoma ovary which improved following appropriate immunomodulation with pulse intravenous methylprednisolone and azathioprine.

Background

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy with widespread and distinctive lesions. NMOSD typically presents as recurrent longitudinally extensive transverse myelitis and optic neuritis. Since the landmark discovery of antiaquaporin-4 antibodies and establishment of their pathogenic role in neuromyelitis optica spectrum disorder, many series of NMOSD have been reported.^{1 2} Though initially described as idiopathic or primary central nervous system inflammatory demyelinating disorder restricted to brain and spinal cord, recent reports have suggested its association with other systemic autoimmune disorders and less often with malignancies.^{3 4} More specifically paraneoplastic NMOSD has been described in association with carcinoma of breast, adenocarcinoma of lung, thymoma, lymphoma, thyroid carcinoma and carcinoid tumour.^5–11 According to a recent review, 34 cases of NMOSD secondary to underlying neoplasm have been described in literature until today with breast carcinoma accounting for approximately one-third of all cases.⁶ To the best of our knowledge, NMOSD in relation to adenocarcinoma of ovary has not been described. Here, we report a patient of NMOSD in association with carcinoma of ovary and briefly review the relevant literature.

Case presentation

A 46-year-old healthy woman with acute onset painless blurry vision bilaterally on February 2016, with no ocular symptoms. The visual loss gradually progressed to inability to recognise faces from 20 m distance over 1 month. She was evaluated at another centre and administered a course of intravenous methylprednisolone. She improved transiently following treatment but deteriorated again. One month later she started having abdominal distension, anorexia and loss of weight when she was re-evaluated. A contrast enhanced CT scan of abdomen revealed bulky ovaries with ascites and deposits over omentum, spleen and mesentery, pleural effusion, mediastinal lymphadenopathy and pulmonary nodules. She was referred to our centre where fine needle aspiration cytology of ovarian mass revealed adenocarcinoma. She was administered five cycles of chemotherapy (carboplatin, paclitaxel) followed by bilateral salpingo-oophorectomy and omentectomy (approximately seven months after onset of vision loss). On second postoperative day, she developed weakness and numbness of left upper and left lower limb which gradually worsened for next 10 days, followed by rapid worsening (over 1 day) to complete quadriparesis and inability to turn around in bed. There was no neck weakness or breathing difficulty. Simultaneously, she also developed sensory loss over limbs and trunk along with painless urinary retention and overflow incontinence. Examination revealed bilateral optic atrophy, severe quadriparesis with brisk deep tendon reflexes and sensory level at C5. A clinical possibility of opticospinal syndrome with paraneoplastic NMOSD was considered and she was evaluated for the same.

Investigations and treatment

Routine haematological and biochemical investigations were normal. AQP4-IgG antibodies were found to be positive by tissue-based indirect immunofluorescence at time of presentation with quadriparesis. Gadolinium enhanced MRI of whole spine and brain revealed signal changes suggestive of demyelination in cervicothoracic cord and a diagnosis of NMOSD was made (figure 1).¹² In view of poor performance status and advanced stage of disease, she was planned for monthly pulses of intravenous methylprednisolone and oral azathioprine (3 mg/kg/day). Intravenous immunoglobulin could not be given for financial restraints. She improved gradually.

Figure 1.

(A) Sagittal T2 weighted images showing long segment hyperintensity involving cervical cord and (B) axial T2 weighted images showing hyperintense signal change involving >75% of cross-sectional area of cord; (C) gadolinium enhanced images showing enhancement of the involved cord region; (D) cellular smears showing clusters of tumour cells ((D) (Giemsa stain, 100×) and (E) (H&E stain, 100×). The cells have moderate pleomorphism, nuclei have coarse chromatin, conspicuous nucleoli and moderate amount of cytoplasm ((F) (Giemsa stain, 200×) and (G) (H&E stain, 200×).

Outcome and follow-up

After 6 months of immunomodulation she was ambulant with support and was planned for radiotherapy and chemotherapy for ovarian adenocarcinoma. However, she was lost to follow-up.

Discussion

Clinical manifestations of NMOSD result from immune mediated attack on aquaporin rich regions of brain (optic nerves, spinal cord, area postrema, posterior hypothalamus) through antiaquaporin 4 and related antibodies. Apart from central nervous system, aquaporin 4 is also expressed on other tissues of body such as intestines, endometrium, kidneys, airways, skeletal muscle and so on. In addition, aquaporin 4 is also expressed on several tumour cells such as carcinoma of breast, adenocarcinoma of lung, thymoma, lymphoma,thyroid carcinoma and carcinoid tumour. It is therefore not surprising that NMOSD may occur in setting of an underlying neoplasm. Despite this, <40 cases of paraneoplastic NMOSD have been described in literature and this is the first case report of NMOSD with adenocarcinoma of ovary.

In two large series, NMOSD is described as paraneoplastic phenomena in 31% and 12.2% of all NMOSD cases, respectively.^{13 14} The clinical picture of paraneoplastic NMOSD was akin to its common counterpart that is, NMOSD without underlying neoplasm as seen in our patient too. The prognosis of paraneoplastic NMOSD seems to be more dismal, presumably due to additional morbidity related to neoplasm itself. The mainstay of treatment in paraneoplastic NMOSD is management of underlying neoplastic process. However for continued improvement in NMOSD symptoms, patients often need additional immunomodulation in the form of pulse methyl prednisolone, intravenous immunoglobulin or other immunosuppressive drugs such as azathioprine, cyclophosphamide or mycophenolate. Most patients show good improvement following treatment of tumour and immunomodulation as was seen in our patient also.

A word of caution needs to be mentioned here. Not all non-compressive myelopathies in setting of neoplastic process are NMOSD. Opticospinal syndrome has been also reported with anti-myelin-oligodendrocyte glycoprotein (MOG), CRMP-5/anti-CV-2 (collapsin response mediator protein) antibodies whereas myelopathy has been described with antiamphiphysin and anti-Hu antibodies.^{6 15–17} Thus, one needs to carry out appropriate laboratory testing to find out source of paraneoplastic myelopathy.

Learning points.

• Our case adds further to expanding repertoire of paraneoplastic neuromyelitis optica spectrum disorder (NMOSD).

• It stresses on the need to recognise this complication urgently in cancer as appropriate immunomodulatory treatment often results in good improvement.

• Our case emphasises the need for neoplasm screening in NMOSD.