Neuroendocrine Carcinoma as a Cause of Humoral Hypercalcemia of Malignancy: A Case of a Patient With Elevated Parathyroid Hormone-Related Protein.

Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome caused by elevations in parathyroid hormone-related protein (PTH-rP). HHM often presents in patients with squamous cell carcinomas of the lung, head, and neck, as well as breast, ovarian, renal, and bladder carcinomas. HHM associated with neuroendocrine carcinoma (NEC) is rarely observed. Here, we report a case of NEC-associated HHM refractory to standard calcium-reducing therapies but improved with the off-label addition of cinacalcet. A 31-year-old male with metastatic NEC presented to the emergency department (ED) with symptoms of nausea, emesis, constipation, and progressive weakness. He was being treated via a clinical trial at a tertiary referral center after failing standard therapies. He had recently been admitted at an outside facility for hypercalcemia, which had been managed with denosumab (120 mg subcutaneously) over the previous four weeks. He was admitted from the ED with a serum calcium of 14.6 mg/dL, potassium of 2.9 mmol/L, and phosphate of 1.2 mg/dL; ionized calcium was elevated at 8.0 mg/dL. Despite hydration and aggressive electrolyte replacement, his calcium increased to 15.5 mg/dL. Further laboratory evaluation revealed parathyroid hormone (PTH) of 6 pg/mL (10-65 pg/mL), 25-hydroxyvitamin D of 25 ng/mL (25-80 ng/mL), 1,25-dihydroxyvitamin D of 513 pg/mL (18-64 pg/mL), and PTH-rP of 25 pmol/L (<2.5 pmol/L), consistent with HHM. Calcitonin was avoided due to a prior hypersensitivity reaction. He received prednisone 10 mg daily and pamidronate 90 mg IV, and his calcium improved to 11.5 mg/dL. He was discharged and investigational therapy was resumed. This therapy failed, and he did not qualify for additional cancer therapy due to refractory hypercalcemia. He was started on cinacalcet, and his calcium decreased enough to permit further cancer treatment. He had multiple hospitalizations with fluctuating calcium levels and ultimately died several months later after sustaining a subarachnoid hemorrhage from a fall. In conclusion, we report a rare case of HHM associated with NEC. While many cases of HHM are effectively managed with hydration, calcitonin, antiresorptive therapies, and glucocorticoids, some are refractory. Our patient was refractory and differed from most patients with HHM in at least two ways. As mentioned previously, NEC causing HHM is quite uncommon (~2% of cases); it is unclear, but this malignancy might predispose to refractory hypercalcemia. Our patient's elevated vitamin D may also have made his HHM more resistant to treatment. Ultimately, while not first line, cinacalcet was an effective treatment in our patient. This provides additional evidence that cinacalcet may be considered for refractory hypercalcemia secondary to malignancy.

Atypical teratoid/rhabdoid tumor involving cerebrospinal fluid: a case report.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, aggressive tumor of the central nervous system. It is primarily seen in younger age-groups, and the cytomorphology has only been infrequently described. CASE: We present a case of AT/RT arising in the cervical spine of a 6-month-old boy. The cerebrospinal fluid (CSF) cytology and correlating findings are described. The CSF cytomorphologic findings of the AT/RT cells are most notably large cells, eccentrically placed pleomorphic nuclei, prominent nucleoli and, commonly, cytoplasmic inclusions, as well as a second population of smaller mononuclear cells with minimal cytoplasm. CONCLUSION: The cervical spine is a rare site for AT/RT to arise. It is important for pathologists to recognize the cytomorphologic features of AT/RT in the CSF of patients with this tumor to help determine prognosis and disease progression.

Cholangiocarcinoma in a 17-year-old boy with primary sclerosing cholangitis and UroVysion™ fluorescent in situ hybridization.

Primary sclerosing cholangitis (PSC) is uncommon in the younger age range and bile duct brushing cytology can present unique challenges. We describe the case of a 17-year-old boy with a new diagnosis of PSC who presented with cholangiocarcinoma. The clinical history, endoscopic features, cytomorphologic findings, and results of UroVysion™ fluorescent in situ hybridization (FISH) on the bile duct brush are described. UroVysion FISH on bile duct brushings is an ancillary study that can improve the diagnostic sensitivity for malignancy, specially in challenging cases where the cytomorphologic or clinical characteristics of the case are not typical. The occurrence of cholangiocarcinoma in young age group with PSC is uncommon, and the utilization of UroVysion FISH has been rarely described.

Check Sample Abstracts.

The following abstracts are compiled from Check Sample exercises published in 2008. These peer-reviewed case studies assist laboratory professionals with continuing medical education and are developed in the areas of clinical chemistry, cytopathology, forensic pathology, hematology, microbiology, surgical pathology, and transfusion medicine. Abstracts for all exercises published in the program will appear annually in AJCP.

Sporadic fatal insomnia masquerading as a paraneoplastic cerebellar syndrome.

BACKGROUND: Sporadic fatal insomnia is a rare prion disease that has recently been recognized. OBJECTIVE: To report a unique case of sporadic fatal insomnia in a woman with progressive cerebellar deterioration who was originally thought to have a paraneoplastic cerebellar syndrome. DESIGN: Case report describing a patient with autopsy-proven sporadic fatal insomnia. PATIENT: A 56-year-old woman with progressive cerebellar ataxia who was found to have a retroperitoneal non-Hodgkin lymphoma. RESULTS: Autopsy demonstrated marked degenerative changes in the thalamus, cerebellum, and inferior olivary nucleus. A mild spongiform change was present in the thalamus and cortical gray matter. Western blot analysis confirmed the presence of abnormal, protease-resistant prion protein (PrP(Sc)), characteristic of sporadic fatal insomnia. CONCLUSIONS: Clinicians should be aware of this rare prion disease and should strongly consider the importance of autopsy toward the investigation of unusual neurological diseases.