Valproic Acid Induced Thrombocytopenia and Dysmegakaryopoiesis in a Pediatric Patient.

OBJECTIVE: Valproic acid (VPA) is an effective first-line anticonvulsant that is associated with several side effects including bone marrow suppression and subsequent cytopenia. However, VPA associated myelodysplasia is not a well described entity that can be seen in patients on VPA treatment. CASE REPORT: Herein, we describe a 9-year-old female patient with a past medical history of seizure disorder who presented with 3-week history of intermittent fevers, fatigue, weakness, and multiple unexplained bruises. Complete blood count (CBC) was remarkable for marked thrombocytopenia. Trephine biopsy showed a normocellular marrow with maturing trilineage hematopoiesis and scattered atypical megakaryocytes including numerous small hypolobated forms with frequent forms showing separated nuclei. Her CBC showed normalization 7 months after VPA was stopped. CONCLUSIONS: The presence of bone marrow suppression and myelodysplasia in patients on VPA treatment should be taken into consideration as it can cause a diagnostic pitfall especially in pediatric and elderly populations. A careful review of past medical history and medications can help make the correct diagnosis.

Malignant Variant of Calcifying Epithelial Odontogenic Tumor with Neuroendocrine Differentiation.

A 60-year-old female presented with asymptomatic failing mandibular dental implants. Computed tomography (CT) showed a partially calcified, hypointense lesion within the soft tissues, measuring 1.3 x 0.8 x 1.0 cm along the buccal cortex. Incisional biopsy demonstrated a basaloid type of tumor composed of sheets of cells with plump ovoid nuclei, distinct nucleoli, and scant eosinophilic cytoplasm. Mitoses were present, averaging about 2 per 10 high power fields with scattered individual apoptotic cells. Numerous laminated calcified bodies (Liesegang rings) were observed with confluence of these bodies to form larger foci of dystrophic mineralization. These features clearly established the malignant nature of this tumor. Immunohistochemically, the tumor was positive for synaptophysin, focally positivity for CAM 5.2 and had a Ki-67 proliferation index of approximately 25%. This is the first report of a tumor with features of a malignant variant of calcifying epithelial odontogenic tumor and neuroendocrine differentiation.

Describing IgA Myeloma: An Immunophenotypic and Molecular Approach.

Plasma cell myeloma (PCM) is defined as a clonal disease of terminally differentiated plasma cells that secrete immunoglobulin. The biologic underpinnings of IgA-type multiple myeloma's (IgAMM) aggressive nature, including its increased morbidity and mortality, have not been elucidated. We describe the clinical, phenotypic, and cytogenetic characteristics of IgA-MM. Flow-cytometry analysis was performed to phenotype clonal plasma cell populations, and interface with fluorescent in situ hybridization (iFISH) to exploit cytogenetics to determine risk stratification; 68.1% of cases were of intermediate or high risk. On flow cytometry, samples from our IgA-PCM cohort revealed less frequent CD56 expression when compared to samples with other PCM subtypes. Our study demonstrated lower frequency of CD56 expression (52.8%). We hypothesize that loss of CD56 may play a significant role in the aggressive behavior of IgA-PCM due to the loss of cell-to-cell adhesion resulting in a higher propensity for extramedullary presentation.

Therapeutic plasma exchange in a patient with acute motor axonal neuropathy subtype of Guillain-Barre syndrome and systemic lupus erythematosus.

A young female in her early 20s with a history of systemic lupus erythematosus presented to the emergency department due to 4 days of progressive bilateral extremity weakness and numbness. The patient reported flu-like symptoms that had spontaneously recovered 2 weeks prior to her presentation. She was 10 weeks pregnant at presentation. Lumbar puncture study and electrical muscle stimulation (EMS) were consistent with acute motor axonal neuropathy subtype of Guillain-Barre syndrome (GBS). Patient also had increased proteinuria and renal biopsy performed that was consistent with lupus nephritis. Despite treatment with pulse dose corticosteroids and IVIG, the patient had minimal neurological improvement and with continued decline required intubation. Her pregnancy was terminated at this point and a course of therapeutic plasma exchange (TPE) was started. Patient was also treated with cyclophosphamide. The patient responded to the combination of therapy and had slow but gradual neurologic recovery as well as improvement of proteinuria. Here we describe a case of an acute motor axonal neuropathy (AMAN) subtype of GBS in a young woman with active SLE and current pregnancy at the time of the presentation. Concurrent GBS and active SLE in the setting of pregnancy may be more treatment resistant, and combination therapy including TPE, immunosuppression, and termination of pregnancy may be indicated.

Long-Term Progression of Sensorineural Hearing Loss and Tinnitus after Combined Intensity-Modulated Radiation Therapy and Cisplatin-Based Chemotherapy for Nasopharyngeal Carcinoma: A Case Report.

Sensorineural hearing loss (SNHL) is a common adverse effect for nasopharyngeal carcinoma (NPC) patients treated with chemoradiotherapy. We report a case of 12-year follow-up from a patient with stage IIB NPC, treated in 2004 with intensity-modulated radiotherapy and cisplatin-based chemotherapy. Pure-tone audiograms were conducted before treatment and at two other points in the 12-year period after treatment. Analysis of the patient's audiograms reveals that the development of high-frequency SNHL started after treatment and reached a plateau accompanied by tinnitus approximately 32 months after treatment conclusion. After the plateau, high-frequency SNHL continued to develop slowly in the next 10 years, possibly a long-term effect from radiation-induced microvascular change of the hearing apparatus. The continuous high-frequency hearing decline is associated with increased tinnitus pitch in the patient. With experience learned from this case, we recommend hearing tests at regular intervals for at least 3-5 years for NPC patients treated with chemoradiotherapy. Patients need to be educated about tinnitus and counseling can be offered when they begin to feel inconvenienced by tinnitus. These patients also need to be advised against exposure to noise that can aggravate the already compromised hearing apparatus, leading to further hearing loss and worsening tinnitus. Limiting the peak dose and total cumulative dose of cisplatin should be considered based on the patients' risk factors to achieve a balance between treatment efficacy and long-term adverse effects.

Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: a 2-year randomized study.

BACKGROUND: Cell-based strategies that combine in vitro- expanded autologous chondrocytes with matrix scaffolds are currently preferred for full-thickness cartilage lesions of the knee ≥2 cm(2). Although this approach is reasonable, continuing advances in the field of cartilage repair will further expand the options available to improve outcomes. HYPOTHESIS/PURPOSE: In the present clinical study, we compared the outcomes of matrix-induced autologous mesenchymal stem cell implantation (m-AMI) with matrix-induced autologous chondrocyte implantation (m-ACI) for the treatment of isolated chondral defects of the knee. STUDY DESIGN: Prospective, single-site, randomized, single-blind pilot study. METHODS: Fourteen patients with isolated full-thickness chondral lesions of the knee >2 cm(2) were randomized into two treatment groups: m-AMI and m-ACI. Outcomes were assessed pre-operatively and 3, 6, 12 and 24 months post-operatively. RESULTS: Clinical evaluations revealed that improvement from pre-operation to 24 months post-operation occurred in both groups (p < 0.05). At all follow-up intervals, m-AMI demonstrated significantly better functional outcomes (motion deficit and straight leg raise strength) than did m-ACI (p < 0.05). At all follow-up intervals, m-AMI demonstrated significantly better subjective sub-scale scores for pain, symptoms, activities of daily living and sport and recreation of the knee injury and osteoarthritis outcome score (KOOS) than did m-ACI (p < 0.05). Additionally, m-AMI demonstrated significantly better (p < 0.05) scores than m-ACI for the quality of life sub-scale of the KOOS and visual analog scale (VAS) severity at the 6-month follow-up. The Tegner activity score and VAS frequency were not significantly different between the two groups. Graft failure was not observed on magnetic resonance imaging at the 24-month follow-up. m-AMI and m-ACI demonstrated very good-to-excellent and good-to-very good infill, respectively, with no adverse effects from the implant, regardless of the treatment. CONCLUSION: For the treatment of isolated full-thickness chondral lesion of the knee, m-AMI can be used effectively and may potentially accelerate recovery. A larger patient cohort and follow-up supported by histological analyses are necessary to determine long-term outcomes.