Aggressive Plasmablastic Myeloma With Extramedullary Cord Compression and Hyperammonemic Encephalopathy: Case Report and Literature Review.

BACKGROUND: Plasmablastic myeloma is an aggressive subtype of multiple myeloma with overall poor prognosis. Spinal cord compression and hyperammonemic encephalopathy are two grave complications of multiple myeloma with significantly poor survival outcomes. CASE REPORT: A 49-year-old male presented with a 5-day history of worsening abdominal distention with inability to walk, urinate or defecate. Imaging findings of innumerable spinal osteolytic lesions with paraspinal masses coupled with a bone marrow biopsy of ≥70% plasmablasts confirmed the diagnosis of plasmablastic myeloma. Despite spinal decompression surgery, the patient remained paraplegic. Three myeloma-directed chemotherapies failed, eventually leading to him developing hyperammonemic encephalopathy culminating in his death. CONCLUSION: Plasmablastic myeloma is a rare entity which poses therapeutic challenges especially in patients with negative prognosticators, including high-risk cytogenetic markers, extraosseous involvement with cord compression and hyperammonemic encephalopathy. Early aggressive management with consideration of novel therapeutic alternatives, especially in treatment refractory disease, can be worthwhile.

Metastatic Paraganglioma of the Spine With SDHB Mutation: Case Report and Review of the Literature.

BACKGROUND: Paragangliomas (PGLs) are rare neuroendocrine tumors that can arise from any autonomic ganglion of the body. Most PGLs do not metastasize. Here, we present a rare case of metastatic PGL of the spine in a patient with a germline pathogenic succinate dehydrogenase subunit B (SDHB) mutation. METHODS: In addition to a case report we provide a literature review of metastatic spinal PGL to highlight the importance of genetic testing and long-term surveillance of these patients. RESULTS: A 45-year-old woman with history of spinal nerve root PGL, 17 years prior, presented with back pain of several months' duration. Imaging revealed multilevel lytic lesions throughout the cervical, thoracic, and lumbar spine as well as involvement of the right mandibular condyle and clavicle. Percutaneous biopsy of the L1 spinal lesion confirmed metastatic PGL and the patient underwent posterior tumor resection and instrumented fusion of T7-T11. Postoperatively the patient was found to have a pathogenic SDHB deletion. CONCLUSIONS: Patients with SDHx mutation, particularly SDHB, have increased risk of developing metastatic PGLs. Consequently, these individuals require long-term surveillance given the risk for developing new tumors or disease recurrence, even years to decades after primary tumor resection. Surgical management of spinal metastatic PGL involves correcting spinal instability, minimizing tumor burden, and alleviating epidural cord compression. In patients with metastatic PGL of the spine, genetic testing should be considered.

Utility of Pit-1 Immunostaining in Distinguishing Pituitary Adenomas of Primitive Differentiation from Null Cell Adenomas.

Pit-1 immunostaining is not routinely used in the characterization of pituitary adenomas, and its utility in distinguishing adenomas dedicated towards the lactotroph, somatotroph, and thyrotroph lineage from null cell adenomas warrants further evaluation. Pituitary adenomas that were negative for expression of a basic panel of hormonal markers (ACTH, prolactin, and growth hormone) were further evaluated for TSH, SF-1, and Pit-1 expression using a tissue microarray. Among the 147 identified pituitary adenomas that were negative for ACTH, prolactin, growth hormone, and TSH, expression of SF-1 was present in 68 cases (46%). Of the remaining 72 cases with sufficient tissue for further analysis, four were Pit-1 positive (6% of the adenomas negative for ACTH, prolactin, growth hormone, TSH, and SF-1); the remaining 68 were potentially null cell adenomas. Two of the Pit-1-positive adenomas displayed a paranuclear CAM 5.2 staining pattern suggestive of a sparsely granulated somatotroph adenoma; however, only one case contained fibrous bodies within a majority of the adenoma cells. Our data suggests that Pit-1 can be utilized as a second tier immunostain in cases of clinically non-functioning adenomas that are immunonegative for ACTH, prolactin, growth hormone, TSH, and SF-1 in order to further segregate rare cases of Pit-1-positive adenomas from null cell adenomas. Pit-1 immunostaining can recognize rare cases of sparsely granulated somatotroph adenomas that appear immunonegative for growth hormone, as well as rare cases of other Pit-1-positive adenomas that are negative for Pit-1 lineage hormones. Overall, pituitary adenomas of the Pit-1 lineage that do not produce prolactin, growth hormone, or TSH are rare, with only four cases identified in the current study.

Structural analysis of a type 1 ribosome inactivating protein reveals multiple L­asparagine­N­acetyl­D­glucosamine monosaccharide modifications: Implications for cytotoxicity.

Pokeweed antiviral protein (PAP) belongs to the family of type I ribosome­inactivating proteins (RIPs): Ribotoxins, which function by depurinating the sarcin­ricin loop of ribosomal RNA. In addition to its antibacterial and antifungal properties, PAP has shown promise in antiviral and targeted tumor therapy owing to its ability to depurinate viral RNA and eukaryotic rRNA. Several PAP genes are differentially expressed across pokeweed tissues, with natively isolated seed forms of PAP exhibiting the greatest cytotoxicity. To help elucidate the molecular basis of increased cytotoxicity of PAP isoenzymes from seeds, the present study used protein sequencing, mass spectroscopy and X-ray crystallography to determine the complete covalent structure and 1.7 Å X­ray crystal structure of PAP­S1aci isolated from seeds of Asian pokeweed (Phytolacca acinosa). PAP­S1aci shares ~95% sequence identity with PAP­S1 from P. americana and contains the signature catalytic residues of the RIP superfamily, corresponding to Tyr72, Tyr122, Glu175 and Arg178 in PAP­S1aci. A rare proline substitution (Pro174) was identified in the active site of PAP­S1aci, which has no effect on catalytic Glu175 positioning or overall active­site topology, yet appears to come at the expense of strained main­chain geometry at the pre­proline residue Val173. Notably, a rare type of N­glycosylation was detected consisting of N­acetyl­D­glucosamine monosaccharide residues linked to Asn10, Asn44 and Asn255 of PAP­S1aci. Of note, our modeling studies suggested that the ribosome depurination activity of seed PAPs would be adversely affected by the N­glycosylation of Asn44 and Asn255 with larger and more typical oligosaccharide chains, as they would shield the rRNA­binding sites on the protein. These results, coupled with evidence gathered from the literature, suggest that this type of minimal N­glycosylation in seed PAPs and other type I seed RIPs may serve to enhance cytotoxicity by exploiting receptor­mediated uptake pathways of seed predators while preserving ribosome affinity and rRNA recognition.