Proptosis with hemiplegia: Unusual presentation of multiple myeloma
Surat Raktadan Kendra and Research Centre, Surat, Gujarat, India
Dr. K Ghosh
Surat Raktadan Kendra and Research Centre, Surat, Gujarat
|How to cite this article:|
Ghosh K. Proptosis with hemiplegia: Unusual presentation of multiple myeloma.J Postgrad Med 2018;64:204-205
|How to cite this URL:|
Ghosh K. Proptosis with hemiplegia: Unusual presentation of multiple myeloma. J Postgrad Med [serial online] 2018 [cited 2020 Jan 22 ];64:204-205
Available from: http://www.jpgmonline.com/text.asp?2018/64/4/204/243043
Multiple myeloma is one of the common hematological malignancies and prevalence of this condition seems to be increasing worldwide. In the present issue of the journal, an unusual presentation of multiple myeloma with left-sided proptosis and hemiparesis is reported. Multiple myeloma and soft tissue plasmacytomas are biologically two different diseases, but both may present with proptosis. Soft tissue myeloma such as solitary bony plasmacytoma is a localized disease with better prognosis, and localized radiotherapy alone often gives good local control of the disease for a long period of time, and as monoclonal proteins in these cases are almost absent or present in very low quantities, hyperviscosity-related neurological presentation is also unknown in these cases. However, multiple myeloma when present as soft tissue tumor usually has a worse prognosis.
The case reported in the present issue of the journal is different; here, the disease is extensive, involving both sides of the brain and the skeletal system. The patient already has renal failure, hypoalbuminemia along with left-sided proptosis. In short, she had multiple myeloma of IgG type with proptosis, hemiparesis, and renal failure because of myelomatous infiltration.
Multiple myeloma progresses through asymptomatic monoclonal gammopathy of uncertain origin (MGUS), smoldering myeloma, and then to multiple myeloma as the neoplastic clone keeps on acquiring certain genetic changes. Aggressiveness of the disease follows secondary genetic events. It has been noted that biallelic deletion of P53 gene on chromosome 17 or some other high-risk molecular pathology along with plasmablastic morphology may be associated with large localized tumors., Why such a disease should present in the orbit and what determines its subsequent progression is not well understood. Such conditions have also not been associated with any inflammatory or infective disease in the eye or orbit. All immunoglobulin subtypes of myeloma have been reported to be associated with proptosis.,,,,, Proptosis has been diagnosed in the majority of the cases after myeloma was diagnosed, but in a proportion of cases diagnosis of proptosis preceded the diagnosis of myeloma. Moreover, depending on the origin of orbital myeloma, the following regions of orbit have been identified: (1) commonest being from the bony wall of superotemporal wall of the orbit, epidural space, and temporal fossa; (2) inside the orbit without invasion of bones; (3) from mucous membrane of the sinuses around the orbit; and (4) those originating from orbital floor infiltrating facial soft tissue. Apart from producing diplopia and ptosis, some of the patients like the one described in this issue also had corneal crystalline deposits which go away as the patient responds to treatment.
Proptosis is largely unilateral as in this case but bilateral ones have also been reported. Myeloma-associated involvement of central nervous system (CNS) may be related to hyperviscosity, metabolic disturbances, bleeding, amylodosis, vasculitis, or infection, not to forget the effects of various drugs and renal failure associated with the disease, but rarely as in the present case this could be because of direct involvement of CNS by myeloma cells. The invading myeloma cells to CNS may arise from the marrow of the calvaria, from the lymphoid tissues of orbit or paranasal sinuses, from the meninges, or from deep brain structure itself (very rarely).
In the present case, cerebrospinal fluid showed no myeloma cells, and there were extensive tumors in the orbit and in both hemispheres of the brain. Hence, by definition it does not fulfill the criteria of CNS myeloma; however, imaging reports are quite convincing. Unless one assumes that the CNS tumor was different from myeloma which is most unlikely.
Bone marrow and serum protein electrophoresis clearly showed that we are dealing with myeloma and not with a strictly localized soft tissue plamacytoma. Work up for other tumors was negative mainly on the basis of imaging studies. Hence, in all likelihood the extensive lesions of the brain were myeloma only, but absence of myeloma cells with such an extensive tumor in brain is surprising. As rightly discussed by the authors, there are no clear-cut guidelines for treatment of myeloma involving brain, and in most of these case reports of proptosis and or brain involvement survival was short even after using chemoradiotherapy. This could be because of the fact that many antimyeloma drugs do not cross the blood–brain barrier. However, cranial irradiation should have been enough to clear the tumor as myelomas are radiosensitive tumors.
There are reports where myeloma lead to CNS involvement after autologous bone marrow transplantation (BMT) for the disease suggesting that there were more resistant and aggressive myeloma cells which were already inhabiting the CNS at the time when the autologous BMT was done and which had the growth advantage following myeloablative chemotherapy.
Even today myeloma remains an incurable disease though every year witnesses release of one or more new antimyeloma drugs in the market. There is no denying the fact that survival in myeloma has tremendously improved following combination of thalidomide-like drugs (newer ones, e.g., lenalidomide, pomalidomide) along with bortezomib-type ubiquitination inhibitor (newer and potent one is being introduced frequently, e.g., carfilozomib, ixazomib) and dexamethasone. Monoclonal antibodies (daratumumab and elotuzumab) have also been introduced for their antimyeloma activity. Even then the disease is difficult to cure. CNS and orbital myeloma being rare present a special problem. Molecular pathology in a large series of such patients is not available, and the best management approach have not been tested in randomized trials. As this type of presentation represents less than 1% of myeloma patients, an international multicentric collaboration is one of the ways to test which of the combination therapies with or without stem-cell transplantation will give the best possible results in orbital myeloma with CNS involvement.
|1||Kumar SK, Rajkumar V, Kyle R, van Duin M, Sonneveld P, Mateos MV, et al. Multiple myeloma. Nat Rev Dis Primers 2017;3:1-20.|
|2||Tahiliani N, Kataria P, Patel A, Kendre P. Proptosis and hemiplegia as an initial manifestations of multiple myeloma. J Postgrad Med 2018;64:243-6.|
|3||Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, et al. International Myeloma Working Group molecular classification of multiple myeloma: Spotlight review. Leukemia 2009;23:2210-21.|
|4||Fassas AB, Muwalla F, Berryman T, Benramdane R, Joseph L, Anaissie E, et al. Myeloma of the central nervous system: Association with high risk chromosomal abnormalities, plama blastic morphology and extramedullary manifestations. Br J Haematol 2002;117:103-8.|
|5||Malik A, Narang S, Handa U, Sood S. Multiple myeloma presenting as bilateral orbital proptosis. Indian J Ophthalmol 2009;57:393-5.|
|6||Hsu Vj, Agarwal M, Chen C-S, Rossi C. IgA plasmacytoma in multiple myeloma. Ophthal Plast Reconstr Surg 2010;26:126-7.|
|7||Galea M, Mc Millan N, Weir C. Diplopia and variable ptosis as the sole initial findings in a case of orbital plasma cytoma and multiple myeloma. Semin Ophthal 2015;30:235-7.|
|8||Trecan G, Dufier JL, Blatrix C, Aftimos G, Saraux H, Thomas M. Bilateral malignant exophthalmia as a manifestation of Ig M multiple myeloma. Sem Hop 1977;53:1867-762.|
|9||Hassikou H, Tabache F, Safi S, Laktaoui A, Hadri L. Orbital involvement in IgD kappa myeloma. J Fr Ophthalmol 2007;30:e6.|
|10||Li K, Ku G, Yan M, Broome E, Kelner M, Wang H-Y. A rare and unique case of aggressive IgE-λ plasma cell myeloma in a 28 year old woman presented initially as an orbital mass. Hum Pathol 2012;43:2376-84.|
|11||Thuro B, Sagiv O, Shinder R, Debnam JM, Ozgur O, Ng JD, et al. Clinical and anatomical location of orbital plasma cytomas. Ophthal Plast Reconstr Surg 2018;34:258-61.|