Cerebrospinal Fluid Cytological Diagnosis in Multiple Myeloma With Leptomeningeal Involvement: A Report of Two Cases.

Multiple myeloma (MM) with central nervous system (CNS) infiltration is uncommon and the diagnosis is more complicated than that of MM. Here we report two cases of CNS MM that was diagnosed by cerebrospinal fluid cytology examination. Cerebrospinal fluid cytology examination can help to detect malignant cells and immunocytochemistry stain is of great value in identifying an unknown tumor. Diagn. Cytopathol. 2017;45:66-68. © 2016 Wiley Periodicals, Inc.

[The significance of expression of isoforms RARa1 and RARa2 in response to medicinal therapy and in evaluation of total survival of patients with primarily detected multiple myeloma].

Introduction: The RARa is a transcription factor playing important role in such processes as proliferation, differentiation and apoptosis of cells in norm and in tumor. At the same time, it is little known about significance of expression of two major products of transcription of gene RARa - isoforms RARa and RARa - in pathogenesis of solid and non-solid tumors, including multiple myeloma. The actual data testify ambiguity of input made by isoforms RARa and RARa into processes of tumor development and progression of malignant tumors. The results: It was established that higher level of expression of isoform RARa in combination with increased expression of isoform RARß (group 1) statistically reliable associated with lesser decreasing of concentration of Bence Jones protein in urine of patients in the result of applied treatment and, therefore, lesser effectiveness of response to standard treatment according protocol M-2 in comparison with group II which included patients with lesser levels of expression of RARa and RARß (32.8% and 62.8% for groups I and II correspondingly; p=0.037). The analysis of indices of survival of examined patients in groups I and II demonstrated that median of total survival of patients from group I was reliably lower than in patients included into group II (30 and 84 correspondingly; p=0.046). Conclusion: The results of study demonstrate that increased level of expression in the first instance of isoform RARa in combination with hyper-expression of isoform RARß but not RARa can have unfavorable significance in case of evaluation of response to medicinal therapy and prognosis of total survival in patients with multiple melanoma.

Antibiotic treatment for bacterial meningitis caused by Listeria monocytogenes in a patient with multiple myeloma.

Multiple myeloma is a hematolymphoid malignancy, and patients with this disorder are frequently complicated by infection. An 80-year-old woman with multiple myeloma was complicated by bacterial meningitis, and was admitted to our hospital in August 2007. She initially received ceftriaxone, but culture of cerebrospinal fluid detected Listeria monocytogenes. Ampicillin was administered, but headache and pyrexia persisted for 2 weeks, and on cerebrospinal fluid examination, the proliferation of polymorphonuclear leukocytes had not resolved. After medication with meropenem was started, the clinical symptoms completely disappeared, and the abnormalities on cerebrospinal fluid examination resolved. The patient ultimately received meropenem for 27 days, resulting in a cure. In conclusion, meropenem is useful to treat bacterial meningitis caused by L. monocytogenes. This agent is indicated when ampicillin shows inadequate effect or if the patient has an allergy to ampicillin.

Myelomatous meningitis.

BACKGROUND: The most frequent nervous system complications of multiple myeloma are peripheral neuropathy and epidural spinal cord compression. Myelomatous meningitis (MM) has been considered rare. The current study was performed to characterize the clinical presentation, treatment, and outcome of MM. METHODS: The study was a case series of 14 patients with cerebrospinal fluid (CSF)-positive MM who were treated at a tertiary care university medical center. RESULTS: Fourteen patients with advanced multiple myeloma were treated with involved-field radiotherapy (to the brain in 5 patients and the spine in 6 patients) and intra-CSF chemotherapy (ventricular in 10 patients and lumbar in 4 patients). The best response to treatment included 6 partial responses and 8 patients with progressive disease. The median duration of response was 2.5 months (range, 0-6 months). Cause of death was progressive neurologic disease in 6 patients, combined systemic and neurologic disease in 6 patients, and systemic disease progression in 2 patients. CONCLUSIONS: MM is rare and morbid entity (6-month neurologic disease progression-free survival rate of 7%), and appears to be no more responsive to treatment than solid tumor carcinomatous meningitis.

Elevated cerebrospinal fluid beta-2 microglobulin as a tumor marker in a patient with myeloma of the central nervous system.

Myeloma involvement of the nervous system is rare. Extensive literature review revealed only a few cases reported from different parts of the world. The presence of CNS symptoms and detection of plasma cells in the CSF is the usual basis of diagnosis. In addition, immunoelectrophoresis and immunofixation for detection of monoclonal protein confirm the diagnosis in some cases, while some authors used flow cytometry and cytogenetic studies on CSF. Reports of multiple myeloma also include unfavorable cytogenetic abnormalities of chromosome 13. We report a case with relapsed CNS multiple myeloma with the detection of elevated beta-2 microglobulin (beta2M) as a tumor marker in the CSF.

The absence of CD56 on malignant plasma cells in the cerebrospinal fluid is the hallmark of multiple myeloma involving central nervous system.

By immunohistochemistry, the CD56-positive myeloma cells were detected in three (38%) bone marrow (BM) and one (13%) cerebrospinal fluid (CSF) samples from eight patients with multiple myeloma involving the central nervous system (CNS MM). Of the three patients with CD56-positive BM myeloma cells, two had CSF myeloma cells negative for CD56. In a control cohort of 84 MM patients without CNS involvement, the BM myeloma cells were CD56-positive in 68 (80%) cases (P < 0.0001). The prevalence of CD56-negative myeloma cells in the BM and CSF of our patients suggests that CD56 downregulation may play a role in the pathogenesis of CNS MM.

Multiple myeloma invasion of the central nervous system.

BACKGROUND: Although neurologic manifestations often complicate the course of patients with multiple myeloma (MM), direct central nervous system invasion is rare. OBJECTIVE: To describe the neurologic symptoms and signs, imaging, cerebrospinal fluid findings, and the clinical course of patients with central nervous system myeloma invasion, all of whom had leptomeningeal myelomatosis. DESIGN AND PARTICIPANTS: Review of 23 patients with MM and leptomeningeal myelomatosis proven by malignant plasma cells in their cerebrospinal fluid. SETTING: Tertiary-care university medical center. RESULTS: Twenty-one patients had advanced-stage MM. Leptomeningeal myelomatosis was diagnosed up to 29 months (median, 13 months) after diagnosis of MM. Symptoms precipitating neurologic evaluation included manifestations of diffuse cerebral dysfunction, cranial nerve palsies, and spinal radiculopathies. Cerebrospinal fluid was abnormal in all patients, usually exhibiting pleocytosis and elevated protein content, plus positive cytologic findings. Specific magnetic resonance imaging findings suggestive of central nervous system invasion were found in 70% of the patients. These included leptomeningeal contrast enhancement and evidence of meningeal-based lesions sometimes masquerading as intraparenchymal lesions. Despite aggressive systemic and local treatment, the outcome was poor, reflecting the aggressiveness of the underlying MM. CONCLUSION: Leptomeningeal myelomatosis, although rare, should be considered in patients with MM and symptoms suggestive of widespread nervous system involvement.