Addison's Disease and Pituitary Enlargement.

A 60-year-old man with Addison's disease, primary hypothyroidism and type 2 diabetes mellitus who was treated with stable doses of hydrocortisone and fludrocortisone developed increasing skin pigmentation and a bitemporal hemianopia. The plasma ACTH level was 14,464 pg/mL, and an invasive pituitary macroadenoma with suprasellar extension was found on magnetic resonance imaging leading to transnasal-transsphenoidal adenomectomy. The tumor demonstrated features of an eosinophilic adenoma and stained uniformly for ACTH. Residual tumor was treated with stereotactic radiotherapy. This case and the 13 cases published previously indicate that primary adrenal failure may predispose to corticotroph hyperplasia, and in some patients to the development of an invasive corticotroph adenoma. The ACTH level should be measured, and a pituitary magnetic resonance imaging is indicated when skin pigmentation increases in a patient with primary adrenal failure who is receiving customary treatment with glucocorticoids and mineralocorticoids.

Surgery for blastomycosis of the spine.

Blastomycosis is a rare fungal infection that primarily produces acute lung infections but may disseminate to multiple sites, including the spine. Once vertebral involvement occurs, an untreated infection may result in vertebral body destruction and paraspinal and epidural abscess formation followed by neurologic injury and loss of structural integrity of the spine. We report the case of a 30-year-old man who had pulmonary blastomycosis (treated with oral itraconazole for 6 months) and presented with a 2-month history of mild thoracolumbar back pain and numbness and tingling in the lower extremities, but no neurologic deficits. Imaging revealed a destructive lesion of T11 with an extensive paravertebral and retropleural abscess tracking a spinal level above and below with extension into the spinal canal. The patient underwent incision and drainage, culture procurement and corpectomy of T11 with autogenous rib graft in a titanium cage, and, 1 week later, posterior fusion and instrumentation. Cultures were positive for Blastomycosis dermatitidis. Oral itraconazole was continued. Blastomycosis that disseminates to the spine may cause serious neurologic and structural complications. In most cases, long-term use of antifungal medication eradicates the infection. Should medical treatment fail, however, surgery is a useful option.

Molecular factors associated with recurrence and survival following hepatectomy in patients with intrahepatic cholangiocarcinoma: a guide to adjuvant clinical trials.

BACKGROUND: This study sought to determine clinical and molecular factors related to recurrence and survival in patients with ICC following hepatectomy. METHODS: Database review identified 34 patients. Molecular markers (Ki67, p53, beta-catenin) and standard pathological evaluations were performed. RESULTS: The most common resections were right (n = 11), extended right (n = 8), and left hepatectomy (n = 7). The 30- and 90 -day mortality rates were 5.9% and 11.8%. The median tumor size was 7.8 cm. Nine patients (26.5%) had positive lymph nodes and ten patients (29.4%) received adjuvant therapy. Median follow up was 33.5 months. The median disease-free interval was 6 months. The median overall survival was 37.9 months. Univariate predictors of recurrence were tumor size (P = 0.02) and differentiation (P = 0.05). On multivariate analysis, differentiation (P = 0.03; OR = 0.38; 95% CI: 0.17-0.89) remained significant. Univariate predictors of survival were tumor size (P = 0.02), lymphovascular invasion (P = 0.02), satellite nodules (P = 0.006), beta-catenin expression (P = 0.008), and recurrence (P = 0.026). On multivariate analyses, satellite lesions (P = 0.05, OR = 3.15, 95% CI: 0.96-10.4) and beta-catenin (P = 0.04, OR = 3.23; 95% CI: 1.1-9.7) remained significant and differentiation (P = 0.045; OR = 0.42; 95% CI: 0.18-0.98) was an additional predictor. CONCLUSION: Future clinical trials could include certain molecular and pathologic factors to assist in determining the necessity and type of adjuvant therapy.

Hepatoid adenocarcinoma of the lung: report of five cases and review of the literature.

The current diagnostic criteria for hepatoid adenocarcinoma of lung include typical acinar or papillary adenocarcinoma and a component resembling hepatocellular carcinoma and expressing α-fetoprotein (AFP). Distinguishing hepatoid adenocarcinoma of lung from hepatocellular carcinoma metastatic to lung is difficult in patients with both lung and liver masses and in patients at risk for lung and liver cancer because of smoking and viral hepatitis, respectively. We studied morphologic features of hepatoid adenocarcinoma of lung and established an immunohistochemical panel to facilitate distinction of hepatoid adenocarcinoma of lung from hepatocellular carcinoma metastatic to lung. Five cases of hepatoid adenocarcinoma of lung were stained with hematoxylin and eosin and mucicarmine for histomorphologic evaluation. The 14-marker immunohistochemical profile was established for hepatoid adenocarcinoma of lung and compared with that of hepatocellular carcinoma. Two cases of hepatoid adenocarcinoma of lung had signet-ring cell components. Three cases were pure hepatoid adenocarcinoma without components of acinar or papillary adenocarcinoma, signet-ring cells or neuroendocrine carcinoma. Like hepatocellular carcinoma, hepatoid adenocarcinoma of lung expresses CK8 (5/5), CK18 (5/5), AFP (3/5) and HepPar1 (5/5), shows cytoplasmic staining with TTF-1 (5/5) and does not express CK14 (0/5). Unlike hepatocellular carcinoma, it expresses CK5/6 (1/5), CK7 (3/5), CK19 (4/5), CK20 (1/5), HEA125 (5/5), MOC31 (5/5), monoclonal CEA (3/5) and napsin A (1/5). An immunohistochemical panel that includes a variety of cytokeratins, monoclonal CEA and EpCAM markers (HEA125 and MOC31) facilitates distinction of hepatoid adenocarcinoma of lung from hepatocellular carcinoma metastatic to lung, especially when correlated with clinical and radiologic findings. We propose modification of the current diagnostic criteria for hepatoid adenocarcinoma of lung. Tumor composition can be either pure hepatoid adenocarcinoma or hepatoid adenocarcinoma with components of typical acinar or papillary adenocarcinoma, signet-ring cells or neuroendocrine carcinoma. AFP expression is not requisite for diagnosis as long as other markers of hepatic differentiation are expressed.

Expression of p16 in sinonasal undifferentiated carcinoma (SNUC) without associated human papillomavirus (HPV).

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon and highly aggressive neoplasm of the paranasal sinuses and nasal cavity. Its undifferentiated histologic appearance often requires immunohistochemical studies to distinguish it from other high-grade neoplasms. Due to the rarity of SNUC, its immunohistochemical staining profile has been incompletely characterized, and little work has been done on its expression of the markers for human papillomavirus (HPV). Our objective is to expand our knowledge of its immunophenotype and its association with HPV in order to define markers with mechanistic potential in the disease process, or of possible therapeutic importance. A total of five patients (one woman and four men) with SNUC, ranging in age from 26 to 75 years (mean 56.8 years) were compared to five patients (five men) with poorly differentiated squamous cell carcinoma (PDSCC), ranging in age from 53 to 75 years (mean 62.2 years). PDSCC was chosen as a control, given its well-reported immunohistochemical profile and negativity for HPV markers. The immunohistochemical panel included: CK7, CK19, EMA, NSE, chromogranin, p53, CK5/6, p63, CK14, S100, HMB-45, desmin, muscle specific actin, and CD45. Additionally, tests for p16, EBV, and HPV (subtypes 6, 11 16, 18) were performed. The diagnosis of SNUC was confirmed in all cases by histology and immunohistochemical stains. An interesting finding of strong diffuse positivity for p16 was noted in all SNUC cases, compared to only two of five PDSCC that were positive for p16. HPV DNA was not detected in any SNUC cases or any cases of PDSCC. All SNUC cases demonstrated over expression of p16 in the absence of HPV DNA expression. This may represent residual epithelial p16 staining, which is normally present in the sinonasal tract. Due to the rarity of SNUC, more cases will need to be evaluated to confirm the absence of HPV DNA.