Is MS the new paraneoplastic disorder?

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The most interesting of scientific discoveries are sometimes hidden in the most obscure of places. In this case an open access journal that I’d never heard of before, and a discussion from the authors that is close but no cigar.

The authors report of a 39-year-old woman who presented with a demyelinating brain lesion, but on further search was found to also have a thymoma (a thyroid cancer). The most interesting finding was that the tumorous cells also contained myelin basic protein that can only be found in the brain (see Figure below).

Figure: Immunohistochemical staining of myelin basic protein (×400). Positive staining was observed in cytoplasm of spindle-like cells in Type AB thymoma

In my opinion this case is supportive evidence that in some instance demyelinating disease can be a paraneoplastic disorder. Paraneoplastic disorders are remote effects of certain malignancies that affect the nervous system, triggered by an autoimmune response to cancer elsewhere in the body.

Figure: Paraneoplastic neurological disorders (AJNR)

Abstract

Respirol Case Rep. 2021 Aug 19;9(9):e0834. doi: 10.1002/rcr2.834. eCollection 2021 Sep.

Myelin basic protein expression in thymoma after methylprednisolone administration for multiple sclerosis

Tomomi Isono Naoko Ose Keisuke Kawasaki Ayumi Shibata Soichiro Funaki Yasushi Shintani 

The relationship between thymic epithelial tumour and demyelinating disease (DD) is unknown and surgical resection has not been optimized. A 39-year-old woman was administrated methylprednisolone for newly diagnosed multiple sclerosis. A thymic tumour was found in the antero-superior mediastinum via computed tomography of the chest. Video-assisted thoracoscopic thymectomy was performed. Histologically, the tumour was diagnosed as Type AB thymoma. Immunohistochemical staining showed positive myelin basic protein (MBP) in the cytosol of spindle cells in the tumour specimen. Germinal centres or lymphocytes infiltration were not noted. Ectopic MBP presentation in thymoma might be correlated with DD.

About the author

Neuro Doc Gnanapavan

23 comments

  • Interesting since the Thymus also produces strings of amino acids or, Peptides such as Thymosin alpha 1 that modulate the immune system and others like Thymosin beta 4 that help repair tissue.

  • So… how does the slow burning cancer theory fit with an MSer’s average life expectancy of about 6 years less than the general population (Canadian cohort)?

    • Immune cells sit on a spectrum of controlling cancers and autoimmunity potential. The ones with autoimmunity potential are also bad at controlling cancers. But, not all cells in a persons immune system are autoimmune so generally most people are fine. However, adding immunosuppressants into this mix complicates matters. For example, if your family is pos for BRAC gene then better not go on immunsuppressants.

    • Majority of thymomas are malignant, you never know until you take them out. In a related autoimmune condition that I look after called myasthenia gravis I’ve found it to be 50:50.

  • It is interesting that this was done by Japanese researchers. Japan is one of those countries which exists in a bit of a scientific bubble because people still mainly publish in Japanese and don’t much care about being read in English. I actually learned Japanese in order to access their literature because they are very advanced in my own field. I do wonder whether there wouldn’t be other insights to be gained by someone who was both fluent in Japanese and an expert in MS and was able to go to Japan to work in a research capacity for some period of time.

    • Interestingly their main research area is neuromyelitis optica, they publish very little on MS.

  • How would you treat this though? Is there a was to treat the cause of this?

    And do you think it maybe something that is worth perusing as the cause of MS?

    • The answer is already there as to treatment option, but understanding how this works is a lot more difficult. Immunosuppression for the former, and for the latter probably starts with genetics, class switching of immune cells and host environemental factors. It’s a piece of the puzzle and the investigators here just happened to do something very random and came across this. Or someone in there group was on a fishing expedition – I would not think of staining for MBP in a thymoma.

    • How can it be explained why more woman have MS than men..?

      Not only ms but all auto immune disease…
      Because women have lower CD8+ t cells…which control EBV

      “An alternative explanation, and the one proposed here, is that a genetic deficiency of CD8+ T cells results in a decreased CD8+ T-cell response to EBV, which allows EBV-infected B cells to accumulate in the target organ.

      The CD4/CD8 T-cell ratio in humans is genetically controlled [62], with at least some of the responsible genes being located in the HLA complex [63]. The CD8+ T cell deficiency and increased CD4/CD8 ratio in autoimmune diseases are also present in the healthy blood relatives of patients with these diseases [36, 45, 46, 64, 65], indicating that the abnormalities are genetically determined and not secondary to the disease process. Interestingly, females generally have lower proportions and numbers of CD8+ T cells, higher proportions and numbers of CD4+ T cells, and higher CD4/CD8 ratios than males [62, 66–70]. These gender differences appear to be hormonally mediated because oestrogen deficiency substantially increases the proportion and number of CD8+ T cells and decreases the CD4/CD8 ratio, with the ratio directly correlating with the serum oestradiol level [71]. Lower numbers of CD8+ T cells in females might contribute to the higher frequency of autoimmune diseases in females than males. Because the number of CD8+ T cells normally declines with increasing age, particularly through childhood [72], but also through adulthood [62, 70, 73], the primary CD8+ T cell deficiency will be aggravated as each person ages, as occurs in patients with MS [74] (Figure 3).

      Proposed genetic deficiency of CD8+ T cells underlying the development of chronic autoimmune diseases. The upper green panel on the graph represents health, the middle orange panel, the development of mild autoimmune disease (mild autoimmunity) and the lower red panel the development of severe progressive autoimmune disease (Severe autoimmunity). In normal individuals (Health) the number of CD8+ T cells declines with increasing age but still remains sufficient to control EBV infection. In individuals with a mild genetic deficiency of CD8+ T cells, the deficiency is aggravated by increasing age eventually leading to insufficient CD8+ T cells to control EBV infection. In individuals carrying HLA class II or class I genes predisposing to specific autoimmune diseases, this leads to the accumulation of EBV-infected B cells in the target organ and the development of autoimmune disease, which progresses in severity as the CD8+ T-cell count further declines with age and as the EBV load in the target organ subsequently increases. In individuals with a severe genetic deficiency of CD8+ T cells, autoimmune diseases develop at a younger age and progress more rapidly. Deprivation of sunlight and vitamin D at higher latitudes aggravates the genetic CD8+ T-cell deficiency and increases the incidence and progression of autoimmune disease.

      https://www.hindawi.com/journals/ad/2012/189096/

    • The patient remains disease free at 12 month follow up without evidence of new lesions. Not on treatment. They’ve called it mild MS. There has been no tumour recurrence as well. Time will tell since the individual is bands positive, I think they’ve missed the boat.

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