Clinical Neuroscience

[Association of temporal lobe inflammatory leukoencephalopathy with two B cell malignancies]

GARZULY Ferenc1, HAHN Katalin2, IVÁNYI János László3, KERESKAI László4, GÁBOR Valéria1, KOVÁCS G. Gábor5, BUDKA Herbert5, KÁLMÁN Bernadette6

MARCH 30, 2014

Clinical Neuroscience - 2014;67(03-04)

[Identification of etiological connections among virtually distinct diseases in a patient may be sometimes challenging. We report a unique case with two B cell malignancies and an inflammatory leukoencephalopathy. Three days prior to admission, the elderly male patient developed fatigue, headaches, recurrent vomiting, memory disturbances, depression and somnolence. Clinical, laboratory and imaging evaluations as well as post mortem histological studies were performed. Simultaneous presence of primary central nervous system B cell lymphoma, temporal lobe inflammatory leukoencephalopathy and multiple (smoldering) myeloma, was revealed by the detailed work up in the treatmentnaïve patient. Based on recent data from genomic studies, we propose that a sequential evolution of molecular pathology lead to the co-occurrence of multiple myeloma and primary central nervous system B cell lymphoma in this patient, and interpret the development of the temporal lobe leukoencephalopathy as a likely paraneoplastic complication of smoldering myeloma.]

AFFILIATIONS

  1. Markusovszky University Hospital, Department of Pathology; Szombathely
  2. Markusovszky University Hospital, Department of Neurology; Szombathely
  3. Markusovszky University Hospital, Department of Hematology; Szombathely
  4. University of Pécs, Institute of Pathology; Pécs
  5. Medical University of Vienna, Institute of Neurology; Austria
  6. Markusovszky University Hospital, Center for Molecular Medicine; Szombathely

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[FOREWORD TO THE PROCEEDINGS OF THE “SELYE SYMPOSIUM - 2013”, HELD AT THE HUNGARIAN ACADEMY OF SCIENCES, BUDAPEST, HUNGARY, MAY 8, 2013]

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[Selye recognized the importance of activation of hypothalamic- pituitary-adrenal axis during stress and the connection between central nervous system and neuroendocrine regulation. This concept basically contributed to initiation of the studies, which revealed the importance of brain gut axis in regulation of gastric mucosal integrity. Several neuropeptides, such as thyreotrop releasing hormones, adrenomedullin, peptide YY, amylin, opioid peptides, nociceptin, nocisatin, substance P, ghrelin, leptin, orexin-A, angiotensin II were shown to induce gastroprotective effect injected centrally. Though the involvement of dorsal vagal complex and vagal nerves in conveying the central action to the periphery has been well documented, additional mechanisms have also been raised. The interaction between neuropeptides further component that may modify the gastric mucosal resistance to noxious stimulus.]

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SZABÓ Sándor

[Although Hans Selye is mostly known for his discovery & development of the stress concept, he also introduced the first physiologically sound, structure-activity classification of steroids that was also based on the chemical structure of steroids in 1943. He not only introduced the names of glucocorticoids & mineralocorticoids but discovered the anti- & pro-inflammatory properties, respectively, of these steroids in animal models. Furthermore, he not only described the first stress-induced gastric ulcers in rats (1936) & characterized the first human ‘stress ulcers’ during the air-raids in London during World War II (1943). Thus, Selye was a much more productive & creative scientist than it is generally considered.]

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[The relationship between stress and mental illness has been extensively studied and there is a growing consensus that the occurrence of mental illness rather depends on a combination of factors than is caused by stressful external events. Significant hypothalamus pituitary adrenal axis abnormalities were observed among others in major depressive disorder and bipolar disorder. In both disorders, the extent of change in cortisol level was related to the severity of illness and to cognitive changes. Exogenous use of synthetic steroids also frequently resulted in severe psychiatric symptoms. In conclusion changes in the level of steroid hormones may cause impairments in the brain.]

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Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

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[Among heamatological diseases, myeloma multiplex is the disease demanding the greatest attention. This statement could refer to the difficulties in diagnosis through the success or failure of a medical treatment and to the unavoidable deterioration of condition caused by complications. The illness, as it is known, is incurable but can be treated for a long period of time. The results of molecular biology offer new possibilities to secure the collection of instruments facilitating future recovery. These new modalities are targeted radiotherapy, the abundance of new drugs attacking the subcellular organellums of affected cells (thalidomid, Neovastat, oblimersen, bortezomib, etc.) and immunotherapy against myeloma cells. The introduction of new therapies, however, is to be permitted only with the greatest caution because the crossing of roads cannot be calculated and this could bring about deterioration too. The delay in theoretical considerations and experience however, allows the possibility to do a critical analysis. The application would become reality after collecting numerous experiences.]

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[We report a case of a 50-year-old male patient, in whom the coexistence of multiple myeloma and diffuse large B cell lymphoma was confirmed. In December 2007, the patient was admitted to the department of internal medicine with fatigue resulting from mild anemia. A tumor of the left testis was discovered, and after semicastration diffuse large B cell lymphoma was diagnosed by histopathological analysis (clinical stage: II/EB). Examination of the bone marrow revealed a plasmocytic infiltrate of 60%, while 36.1 g/l IgG-kappa paraprotein was found in the peripheric blood, fulfilling the diagnostic criteria of multiple myeloma (Durie-Salmon stage: I). The patient received six cycles of rituximab- CHOP-21 chemotherapy for diffuse large B cell lymphoma. Following a transient improvement, the multiple myeloma showed progression, therefore we switched to VTD protocol (bortezomib, thalidomid, dexamethason). The patient underwent high dose chemotherapy and autologous hematopoietic stem cell transplantation. Both hematologic diseases showed complete remission. Both tumour samples were tested for immunoglobulin heavy-chain rearrangement by polymerase chain reaction and DNA sequence analysis, according to which the possibility for clonal relationship between multiple myeloma and diffuse large B cell lymphoma could not be confirmed.]