A refractory human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis patient with lymphoma-type adult T-cell leukemia/lymphoma: A case report and review of the literature

Abstract

Rationale: Adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are caused by HTLV-1, but the coexistence of both disorders is rare. The estimated incidence is approximately 3%.

Patient concerns: A 54-year-old man was unable to stand up because of spastic paraparesis 1 month after the onset. He developed lymphadenopathy in the left supraclavicular fossa 5 months after the onset. The spastic paraplegia and sensory symptoms below the thoracic spinal cord level worsened.

Diagnoses: Both blood and cerebrospinal fluid (CSF) tests were positive for anti-HTLV-1 antibodies. The patient was diagnosed with rapidly progressive HAM/TSP. He was also diagnosed with lymphoma-type ATL by the biopsy specimen of the lymph node. CSF examination at the time of symptom exacerbation showed abnormal lymphocytes, suggesting central infiltration of the ATL in the central nervous system.

Interventions: Methylprednisolone pulse therapy and oral prednisolone maintenance therapy were administered for rapidly progressive HAM/TSP. Intrathecal injection of methotrexate was administered for the suggested central infiltration of the ATL.

Outcomes: Methylprednisolone pulse therapy and intrathecal injection of methotrexate did not improve the patient's exacerbated symptoms. Five months later, clumsiness and mild muscle weakness of the fingers appeared, and magnetic resonance imaging showed swelling of the cervical spinal cord. Clonality analysis showed monoclonal proliferation only in the DNA of a lymph node lesion, but not in the CSF and peripheral blood cells.

Lessons: This was a case of rapidly progressive HAM/TSP associated with lymphoma-type ATL that was refractory to steroids and chemotherapy. The pathogenesis was presumed to involve ATL cells in the brain and spinal cord because of the presence of abnormal lymphocytes in the CSF, but DNA analysis could not prove direct invasion. This case suggests that when we encounter cases with refractory HAM/TSP, it should be needed to suspect the presence of ATL in the background.

Figure 1

Flow cytometric analysis for ATL cells in CSF viable cells (PI−) were selected first (A). Viable cells include 2.34% CD4+ T cells (CD3+, CD4+ fraction) (B). CD4+ T cells include 0.29% ATL cells (CADM1+CD7− cells). This result is not the profile of the ATL. ATL = adult T-cell leukemia/lymphoma, CSF = cerebrospinal fluid.

Figure 2

Contrast-enhanced cervical thoracic spine MRI A very faint hyperintensity is suspected on T2WI from the cervical spinal cord to a part of the middle thoracic spinal cord (both lateral cords to part of the posterior cord). Compared to MRI 6 months earlier, this finding is more evident in the cervical cord. No abnormal contrast findings were observed. MRI = magnetic resonance imaging, T2WI = T2-weighted imaging.

Figure 3

PET-CT In the regions of the bilateral accessory nerves, left lower inner deep neck, left submandibular, and bilateral supraclavicular fossae, lymphadenopathy, and abnormal FDG accumulation were observed. The left supraclavicular lymphoma lesion had shrunk compared to the lesion 8 months earlier, but multiple lymphoma lesions newly appeared. In addition, there is an increase in accumulation in the cervical spinal cord, and there is a region where the increase is particularly strong at the C4 level. These findings suggest the presence of cervical cord infiltration. There is also localized abnormal accumulation in the lower thoracic spinal cord, which might have infiltrated. FDG = fluorodeoxyglucose, HTLV-1 = human T-cell leukemia virus type 1, PET–CT = positron emission tomography–computed tomography.

Figure 4

Clonality analysis of HTLV-1 infected cells. The Cvs of PBMC, CSF cells, lymph node, and monoclonal HTLV-1 infected cell line (TL-Om1) are shown. The Cvs of PBMC and CSF cells were low, whereas the Cvs of the lymph node were high (0.94), suggesting that ATL cells could not be detected in PBMC and CSF cells, whereas ATL cells were dominant in the lymph node. ATL = adult T-cell leukemia/lymphoma, CSF = cerebrospinal fluid, Cvs = clonality values, HTLV-1 = human T-cell leukemia virus type 1, PBMC = peripheral blood mononuclear cell.