Hand Involvement in Ollier Disease and Maffucci Syndrome: a Case Series

Ollier Disease and Maffucci Syndrome are two rare diseases that can cause tumors in several organs, having a special predilection for the hand. However, there have been very few reports in the literature focusing on hand manifestations of these diseases. We report the cases of three female patients: one with Ollier Disease, and two other with Maffucci Syndrome. All patients had hand involvement as their initial primary complaint. The Ollier Disease patient developed chondrosarcomas of two digits and had to have these fingers amputated. One of the Maffucci patients died one year after presentation from a brain glioblastoma. These cases emphasize the importance of early diagnosis of Ollier Disease and Maffucci Syndrome, as these two conditions are associated not only to crippling hand deformity, but also to a significant risk of chondrosarcoma, and other malignant tumors.

Pancreatic Involvement by Plasma Cell Neoplasms

INTRODUCTION: Pancreatic involvement by plasma cell neoplasms is an extremely rare event, with only 50 cases described in the literature. They can present as a primary solitary extramedullary plasmacytoma or plasmacytoma secondary to a plasma cell myeloma. Clinical manifestations are due to the presence of a pancreatic mass usually in the pancreas head, which causes extra-biliary obstruction and abdominal pain. METHODS: Abdominal imaging including CT scan or endoscopic ultrasound with fine-needle aspiration tissue sampling is essential for the initial diagnostic procedure. However, immunohistochemical analysis of the biopsy specimen or flow cytometry of the aspirated material is crucial to prove the monoclonality and the final diagnosis of a plasma cell neoplasm. DISCUSSION: Management of these situations include radiotherapy, chemotherapy, surgery or combined therapy. Novel medications including the immunomodulatory drugs or the proteasome inhibitors followed by consolidation with intensive chemotherapy and haematopoietic stem cell transplantation are nowadays used as upfront treatment in the cases associated to a plasma cell myeloma. CONCLUSION: Despite the rarity, plasma cell neoplasms should be considered in the differential diagnosis of obstructive jaundice and pancreatic neoplasms since they are potentially treatable situations.

Novel FGFR1 Mutations in Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism: Evidence for the Involvement of an Alternatively Spliced Isoform

OBJECTIVE: To determine the prevalence of fibroblast growth factor receptor 1 (FGFR1) mutations and their predicted functional consequences in patients with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: Cross-sectional study. SETTING: Multicentric. PATIENT(S): Fifty unrelated patients with IHH (21 with Kallmann syndrome and 29 with normosmic IHH). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patients were screened for mutations in FGFR1. The functional consequences of mutations were predicted by in silico structural and conservation analysis. RESULT(S): Heterozygous FGFR1 mutations were identified in six (12%) kindreds. These consisted of frameshift mutations (p.Pro33-Alafs*17 and p.Tyr654*) and missense mutations in the signal peptide (p.Trp4Cys), in the D1 extracellular domain (p.Ser96Cys) and in the cytoplasmic tyrosine kinase domain (p.Met719Val). A missense mutation was identified in the alternatively spliced exon 8A (p.Ala353Thr) that exclusively affects the D3 extracellular domain of FGFR1 isoform IIIb. Structure-based and sequence-based prediction methods and the absence of these variants in 200 normal controls were all consistent with a critical role for the mutations in the activity of the receptor. Oligogenic inheritance (FGFR1/CHD7/PROKR2) was found in one patient. CONCLUSION(S): Two FGFR1 isoforms, IIIb and IIIc, result from alternative splicing of exons 8A and 8B, respectively. Loss-of-function of isoform IIIc is a cause of IHH, whereas isoform IIIb is thought to be redundant. Ours is the first report of normosmic IHH associated with a mutation in the alternatively spliced exon 8A and suggests that this disorder can be caused by defects in either of the two alternatively spliced FGFR1 isoforms.