Anti-Hu antibody associated paraneoplastic neurological syndrome in a child with ganglioneuroblastoma: A rare case report and literature review.

RATIONALE: Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens. PATIENTS CONCERNS: Diagnosis and treatment of Hu-PNS. DIAGNOSES: This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination. INTERVENTIONS: The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy. OUTCOMES: The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence. LESSONS: Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.

Immunohistochemical expression of CD44s in human neuroblastic tumors: Moroccan experience and highlights on current data.

BACKGROUND: Peripheral neuroblastic tumors (pNTs), including neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN), are extremely heterogeneous pediatric tumors responsible for 15 % of childhood cancer death. The aim of the study was to evaluate the expression of CD44s ('s': standard form) cell adhesion molecule by comparison with other specific prognostic markers. METHODS: An immunohistochemical profile of 32 formalin-fixed paraffin-embedded pNTs tissues, diagnosed between January 2007 and December 2010, was carried out. RESULTS: Our results have demonstrated the association of CD44s negative pNTs cells to lack of differentiation and tumour progression. A significant association between absence of CD44s expression and metastasis in human pNTs has been reported. We also found that expression of CD44s defines subgroups of patients without MYCN amplification as evidenced by its association with low INSS stages, absence of metastasis and favorable Shimada histology. DISCUSSION: These findings support the thesis of the role of CD44s glycoprotein in the invasive growth potential of neoplastic cells and suggest that its expression could be taken into consideration in the therapeutic approaches targeting metastases. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1034403150888863

Disaloganglioside GD2 loss following monoclonal antibody therapy is rare in neuroblastoma.

BACKGROUND: Gangliosicle GD2 is abundant on human neuroblastoma (NB). Monoclonal antibody 3F8 targeted to GD2 may have imaging and therapeutic potential. Antigen-negative clones can escape immune-mediated attack leading to clinical resistance or recurrence. PROCEDURE: Among 95 evaluable patients treated intravenously with 3F8 (94 Stage 4, 1 Stage 3), 66 received nonradiolabeled 3F8, 11 received 131-iodine-labeled-3F8 (8-28 mCi/kg) with autologous bone marrow rescue, and 18 received both forms of treatment. Prior to treatment, 90 patients tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 68), tumor immunohistochemistry (n = 20), or diagnostic radioimmunoscintigraphy (n = 2). RESULTS: Of 62 patients who had refractory or recurrent neuroblastoma following 3F8 treatment, 61 (98%) tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 51) or tumor immunohistochemistry (n = 10). The sole tumor that lost GD2 expression underwent phenotypic transformation into a pheochromocytoma-like tumor. CONCLUSIONS: The persistence of GD2 expression in refractory or recurrent NB suggests that complete antigen loss is an uncommon event and cannot account for treatment failure.

Autoaggressive inflammation of the myenteric plexus resulting in intestinal pseudoobstruction.

After a 3-year history of severe constipation, a 16-year-old girl required surgery to be relieved of impacted stools. Histologic examination showed ganglionitis in the myenteric plexus of the large bowel and ileum, whereas the submucosal plexus was spared. At this time, antineuronal nuclear antibodies (ANNA-1, anti-Hu) were found at high titer in the serum of the patient. One and a half years earlier, a paravertebral ganglioneuroblastoma had been removed. Histologic examination had shown undifferentiated neuroblasts and morphologically mature ganglion cells with both cell types embedded in an inflammatory infiltrate morphologically similar to the lymphoplasmocytic infiltration seen in the myenteric plexus. The patient's serum was found to bind to nuclei of mouse intestinal tract neurons, thus fulfilling defining criteria for ANNA-1. The serum also reacted with antigens of defined molecular weight in a Western blot, thus fulfilling defining criteria for anti-Hu. Expression of the Huantigen could be visualized in the nuclei of the patient's tumor cells by immunohistochemistry. These tests showed that an antitumor inflammatory response was the cause of the bowel disease. This is the first report of a tumor from the neuroblastoma group that caused paraneoplastic intestinal pseudoobstruction. Ganglionitis and subsequent aganglionosis are the hallmark of the morphologic diagnosis which cannot be obtained by suction biopsy in patients with intact submucosal plexus. Instead, serum testing for autoantibodies can reveal the etiology.