Robert D. Hamilton

What causes a prolactinoma to be aggressive or to become a pituitary carcinoma

INTRODUCTIONMalignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death.CASE REPORTA 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 × 3 × 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725–891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery.CONCLUSIONHeadaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.

Malignant Seeding of Percutaneous Endoscopic Gastrostomy Tract in Patient With Head and Neck Cancer

Malignant seeding of the percutaneous endoscopic gastrostomy (PEG) stoma is a rare and unusual complication of PEG performed in patients with head and neck cancer. Direct seeding of PEG stoma is believed to be the culprit. We present one such case of metastasis that lends support to an alternate hypothesis of vascular spread. First responders in such cases are usually not gastroenterologists and may include dieticians, primary care physicians, and radiologists. As such, we also provide pictures that would help the health care providers recognize this rare entity and manage appropriately and promptly.

Prognostic biomarkers for HNSCC using quantitative real-time PCR and microarray analysis: β-tubulin isotypes and the p53 interactome

In 2014, more than 40,000 people in the United States will be diagnosed with head and neck squamous cell cancer (HNSCC) and nearly 8400 people will die of the disease (www.cancer.org/acs/groups). Little is known regarding molecular targets that might lead to better therapies and improved outcomes for these patients. The incorporation of taxanes into the standard cisplatin/5‐fluouracil initial chemotherapy for HNSCC has been associated with improved response rate and survival. Taxanes target the β‐subunit of the tubulin heterodimers, the major protein in microtubules, and halt cell division at G2/M phase. Both laboratory and clinical research suggest a link between β‐tubulin expression and cancer patient survival, indicating that patterns of expression for β‐tubulin isotypes along with activity of tumor suppressors such as p53 or micro‐RNAs could be useful prognostic biomarkers and could suggest therapeutic targets.

Outcomes utilizing intensity-modulated radiotherapy in oropharyngeal cancers: Tonsils versus base of tongue

The purpose of this study was to present the outcomes of oropharyngeal cancers treated with intensity‐modulated radiotherapy (IMRT) especially the differences between tonsillar and base of tongue (BOT) primaries.

Saving the hand: role of multimodality therapy for Ewing's sarcoma family tumor of the palm

The Ewing’s sarcoma family of tumors (EFTs) are a rare subtype of tumor that include primitive neuroectodermal tumors (PNETs), typical Ewing’s sarcoma, and atypical Ewing sarcoma. EFTs of the hand are extremely rare, and none have been reported to our knowledge beyond the fifth decade of life. EFTs present most frequently in the second decade of life and have a male predominance. Multimodality therapy is typically used to treat patients. We present a case that is unique for several reasons. First, this patient presented in the sixth decade of life, which is later than most cases. Second, treatment included an amputation-sparing resection followed by adjuvant radiation therapy with electron beams. The patient was left with complete functionality of the hand and remained free of recurrent disease 4 years later.

Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With Familial Adenomatous Polyposis.

Background: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. Results: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.