Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma Presenting with Hypercalcemia

Background: Malignancy-associated hypercalcemia (MAHC) occurs in 20-30% of cancer patients and is a common cause of hypercalcemia among hospitalized patients. Its pathophysiology is generally based on bone metastases or the production of parathyroid hormone-related peptide (PTHrP) by tumor cells. The secreted PTHrP causes hypercalcemia via increased calcium absorption at the kidney and increased bone resorption. Here, we present a rare case of combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma (NEC) presenting with hypercalcemia. Case History: A 67-year-old male with a past medical history of alcohol abuse and previously treated Hepatitis C infection in 2012 with ledipasvir/sobosbuvir, was referred to our hospital for evaluation of hypercalcemia. Patient was in his usual state of health until 3 weeks ago when he started having fatigue, nausea, and anorexia. This was also associated with impaired memory and confusion. He was seen at an outside hospital and was found to have a calcium of 16.1 mg/dL (normal range 8.5-10.2 mg/dL), so he was given IV fluids, zoledronic acid and calcitonin with improvement in calcium to 10.8 mg/dL. Computerized tomography (CT) scan of chest/abdomen/pelvis showed a cirrhotic liver and a 6.5 cm hypodense mass within the left hepatic lobe. CT thoracolumbar spine was negative for lytic or blastic lesions with no acute fracture or dislocation. Patient was stabilized and transferred to our hospital for escalation of care. His parathyroid hormone (PTH) was low at 8 pg/ml (15-65 pg/ml) and PTHrP was high at 105 pg/ml (14-27 pg/ml). Repeat imaging with MRI showed a 17 x 8 cm area of signal abnormality with 2 more focal anomalies within, suspicious for malignancy which may be infiltrative. MRI thoracolumbar was negative for any metastasis, fractures or lytic lesions. Skeletal series was also negative for lytic lesions. Microscopic evaluation of the CT-guided liver biopsy showed two distinct patterns. A typical moderately differentiated HCC and a second malignant focus composed of hyperchromatic small to intermediate sized cells with apoptosis, atypical mitoses, vaguely palisading tumor cells around foci of necrosis. This second focus stained positively with CD56 and CAM 5.2 was suggestive of neuroendocrine differentiation and epithelial lineage. Background hepatic parenchyma showed early cirrhosis likely secondary to long standing hepatitis C or due to alcohol abuse. Tumor markers including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA 19-9) were all negative. His workup was negative for another primary malignancy. His disease course was complicated by altered mental status and Klebsiella pneumoniae bacteremia. His PTHrP increased to 335 pg/ml. He received supportive care and expired 3 weeks from initial presentation. Conclusion: Primary HCC and NEC generally tend to have a poorer prognosis than conventional HCC. To our knowledge, this case is the second report of primary mixed HCC and NEC associated with MAHC caused by the production of PTHrP.https://scholarlycommons.henryford.com/merf2020caserpt/1054/thumbnail.jp

Hypoxia-inducible factor in cancer angiogenesis: structure, regulation and clinical perspectives.

Tumor hypoxia is a common feature of many cancers. A master regulator of hypoxic response is the transcription factor hypoxia-inducible factor-1 (HIF-1). It functions as a master regulator of oxygen and undergoes conformational changes in response to varying oxygen concentrations. In this paper, we review what has been described about HIF-1: its structure, its regulation and target genes, its role in cancer, and its implication for cancer therapy.Journal ArticleReviewinfo:eu-repo/semantics/publishe

Successful Management of Hydroxyurea-induced Leg Ulcers in Essential Thrombocythemia: Report of 3 Cases

Essential thrombocythemia is one of the myeloproliferative neoplasms with a plethora of thrombohemorrhagic complications. Hydroxyurea has been proven to be an effective treatment for this condition. However, it is not without side effects. We herein report 3 patients with essential thrombocythemia treated with hydroxyurea who developed refractory leg ulcers, and we outline their successful management. We also review the literature to shed light on the mechanism of this toxicity. Awareness of this important treatment complication is important to avoid the pitfall of futile invasive interventions

Successful treatment of hydroxyurea-associated chronic leg ulcers associated with squamous cell carcinoma

Hydroxyurea (HU) is an antineoplastic drug used in the treatment of chronic myeloproliferative neoplasms (MPNs). HU is associated with cutaneous adverse effects, whereas severe complications such as leg ulcers and non-melanoma skin cancers (NMSCs) are rare and only observed after long-term treatment. We herein report a patient with essential thrombocythemia (ET) treated chronically with HU, and who developed refractory bilateral leg ulcers complicated by squamous cell carcinoma (SCC) over both heels. The patient was successfully managed by multiple debridement stages and skin grafting surgeries. Keywords: Essential thrombocythemia, Hydroxyurea, Squamous cell carcinom