A pulmonary hypertension model induced by continuous pulmonary air embolization.

BACKGROUND: Our goal was to create a clinically relevant large animal model of pulmonary hypertension to serve as a platform allowing preclinical risk/benefit assessment of innovative therapies including artificial lung prototypes. METHODS: Small amounts of filtered air were continuously infused into the pulmonary circulation of sheep (n = 4) for 8 wk. Hemodynamics and blood gases were measured daily. After termination of air embolization, the sheep were observed for 1 additional wk to assess the constancy of the pulmonary artery pressure changes. At the end of wk 9, all sheep were sacrificed and necropsy was performed. RESULTS: All animals survived the study and developed pulmonary hypertension by wk 5. Mean pulmonary artery pressures were elevated from 14 ± 1 at baseline to 35 ± 1 mmHg at wk 8 (P < 0.01) and remained unchanged throughout wk 9. A similar increase in pulmonary vascular resistance was observed. Systemic arterial pressure and PaO(2) dropped slightly compared with baselines but remained in safe ranges. Histologic evidence of severe pulmonary arterial remodeling and significant right ventricle hypertrophy was observed. CONCLUSIONS: We conclude that our 8-wk model of continuous air embolization produces reliable, chronic pulmonary hypertension in sheep with sustained hemodynamic changes, significant pulmonary vascular remodeling, and right ventricle hypertrophy.

Bilateral extensive ductitis obliterans manifested by bloody nipple discharge in a patient with long-term diabetes mellitus.

Ductitis obliterans or mastitis obliterans is a rare late manifestation of mammary ductal ectasia. We describe a long-term diabetic patient who presented with bilateral bloody nipple discharge and poorly defined nodularities around the nipple of both breasts. The ductography showed multiple segments of irregular ductal narrowing and intraluminal filling defects in both breasts. The bilateral resection of the sub-areolar portion of the breast showed exuberant fibrous obliteration of the large- and medium-sized ducts by granulation tissue associated with few histiocytes. Ductal dilatation and intraductal accumulation of histiocytes was also present. This represents a late and florid form of mammary ductal ectasia. Differential diagnostic considerations including fibrocystic changes, diabetic sclerosing lymphocytic lobulitis, idiopathic granulomatous lobular mastitis, and periductal mastitis (Zuska disease) are discussed. Accurate diagnosis can help avoid or limit radical surgeries in this group of patients.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is an extremely rare pulmonary lesion, with only 39 cases reported in the literature. We report an additional case and review the literature. The patient is a 41-year-old man with a 5-year history of progressive dyspnea, cough, and wheezing. He was initially diagnosed as having bronchial asthma but did not respond to treatment of bronchodilators and inhaled steroids. Pulmonary function tests showed airflow obstruction. Chest computed tomography revealed a mosaic pattern of air trapping and thickening of bronchial walls. Open lung biopsy showed diffuse proliferation of pulmonary neuroendocrine cells within the bronchiolar epithelium, often bulging into or obliterating the bronchiolar lumen. These cells also breached the basement membrane, forming tumorlets. There was prominent peribronchiolar fibrosis and obliterative bronchiolitis. The pathologic evaluation of lung tissue is currently the gold standard in making a definitive diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, and all the reported cases were diagnosed by either open lung biopsy or lobectomy.

Immunohistochemical and ultrastructural analysis of a poorly differentiated pediatric age Sertoli-Leydig cell tumor.

Ovarian Sertoli-Leydig cell tumors (SLCT) are rare in young women. They are divided into six categories based on the degree of differentiation and the presence of heterologous elements. Less than 15% of these tumors are poorly differentiated. A 14-year-old obese African-American girl presented with amenorrhea, progressive abdominal pain, and increasing abdominal girth. Pelvic CT revealed a 10 x 9 x 9 cm right adnexal mass which was resected successfully. The gross appearance was dark tan and red with central hemorrhage and necrosis. Microscopically, this was poorly differentiated with compact aggregates of moderate size oval to elongated cells separated by zones of edematous stroma containing scattered spindle shape cells. Areas of ill-formed tubules and primitive cords were present. Clusters of Leydig cells were observed. The oval and spindle cells showed multiple mitoses and were diffusely positive for inhibin and patchy but strong positivity for calretinin. Both preoperative and postoperative studies revealed no metastases. Serum alpha-fetal protein (AFP), androgen, and dihydroepiandrosterone sulfate (DHEA-S) were elevated.

ARDS and diffuse alveolar damage: a pathologist's perspective.

Diffuse alveolar damage (DAD) is the histologic correlate of most patients with adult respiratory distress syndrome (ARDS). It is a relatively straight forward diagnosis and the main differential diagnosis clinically is acute pneumonia and histologically is bronchiolitis obliterans and organizing pneumonia (BOOP). The histologic progression of DAD includes 3 phases (exudative, proliferative, and fibrotic) that correlate with the time rather than its specific cause. The factors that govern which patients will do well and which will develop a fulminant course is not known.

Activation of the hedgehog pathway in a subset of lung cancers.

Activation of the hedgehog pathway is reported in lung cancer, but its frequency remains unknown. We examine activation of this pathway in lung cancers by in situ hybridization and immunohistochemstry, and find that less than 10% of the tumors have elevated hedgehog target gene expression. We further identify a cell line NCI-H209 and two primary tumors with no detectable Su(Fu), a negative regulator of the pathway. Ectopic expression of Su(Fu) in NCI-H209 cells down-regulates hedgehog target gene expression and leads to inhibition of cell proliferation. These data indicate that activation of the hedgehog pathway is activated through Shh over-expression or Su(Fu) inactivation in only a subset of lung cancers.

Leiomyosarcoma of the inferior vena cava: three case reports and review of the literature.

We describe 3 cases of leiomyosarcoma of the inferior vena cava (IVC) and review the literature describing clinicopathologic features of 211 cases and the outcome. Of these, 74% of the cases affected women with median age of 52 years. The most common symptoms were abdominal pain or mass (57%), Budd-Chiari syndrome (17%), and deep vein thrombosis (4%). The most frequent site of tumor origin is the middle segment of the IVC (33%). Tumor size ranged from 2 to 38 cm (mean, 12 cm). Of the tumors with an assigned grade, 46% were high grade, 17% were intermediate grade, and 36% were low grade. Of all patients, 47% underwent complete resection, 24% had complete resection with preoperative or postoperative chemotherapy and/or radiation, and 5% had palliative surgery. Tumor recurrence occurred in 40% of the patients (11% had local recurrence and 29% had metastasis). Perioperative mortality occurred in 4% of the cases. Of those patients who died, 42% died of the disease, 2% died of other causes, 26% were alive and free of the disease, 14% were alive with recurrent disease, and 11% were lost to follow-up. Tumors involving level 2 of the IVC have the best prognosis and tumors of level 1 have the worse prognosis. Although there is no standardized criteria for the grading of extrauterine leiomyosarcoma, we propose to grade based on mitotic activity as follows: high grade, 10 or more mitoses per 10 high-power field (HPF); intermediate grade, 5 to 9 mitoses per 10 HPF; and low grade, 1 to 4 mitoses per 10 HPF.

Adrenocortical carcinoma with concomitant myelolipoma in a patient with hyperaldosteronism.

We present a case of aldosterone-secreting adrenocortical carcinoma with concomitant myelolipoma. To the best of our knowledge, this is the first such reported case. The patient was a 43-year-old man with severe hypertension. Clinical workup revealed an increased serum aldosterone level, hypokalemia, and metabolic alkalosis, and a left adrenal mass was found on computed tomography. The patient underwent a unilateral adrenalectomy, which led to improvement in blood pressure, the serum potassium level, and aldosterone concentration. The tumor weighed 70 g and measured 5.0 cm. On microscopic examination, we found necrosis, focal cytologic atypia, diffuse eosinophilic cells comprising more than 75% of the tumor, 5 to 7 mitotic figures per 50 high-power fields, rare atypical mitosis, and venous invasion. At the periphery of the tumor but within the capsule, microscopic areas of myelolipoma were seen. Ki-67 staining was positive in 20% of the tumor cells. Although rare, aldosterone-secreting carcinoma associated with myelolipoma should be included in the differential diagnosis of adrenal gland masses.

Renal cell carcinoma metastatic to Hurthle cell adenoma of thyroid.

Metastases to the thyroid gland are a common finding at autopsy in patients who died of malignancy and are often misdiagnosed as primary thyroid neoplasms clinically. We present a patient with a rare, unusual case of renal cell carcinoma (RCC) metastatic to a Hurthle cell adenoma of the thyroid. A 53-year-old woman was admitted to a University of Texas Medical Branch Hospital (Galveston, TX) for a large right thyroid mass that was present for 3 months. A fine needle aspiration of the thyroid mass was performed and interpreted as suggestive of a Hurthle cell neoplasm. A total thyroidectomy revealed Hurthle cell adenoma containing clusters of cytologically atypical cells with clear cytoplasm. Subsequent patient evaluation and computed tomography revealed a renal mass. Left radical nephrectomy was performed at a later date for left renal mass and the microscopic examination confirmed the diagnosis of primary clear cell carcinoma of the kidney. Further studies confirmed that the thyroid mass was metastases from RCC. Although carcinoma of the kidney is responsible in most instances of metastatic disease to the thyroid, metastatic RCC to a thyroid neoplasm is extremely rare, with only two reports found in the English literature. The possibility of metastatic RCC should always be taken under consideration, especially when nests of clear cells are seen infiltrating into the thyroid parenchyma or neoplasm.

Multiple Langerhans cell nodules in an incidental thymectomy.

The isolated appearance of Langerhans cell histiocytosis in the thymus is quite rare. We report the finding of multiple small Langerhans cell nodules in the thymus of an 11-month-old infant who had undergone thymectomy in the course of surgical correction of tetralogy of Fallot. The subtle appearance of some of these nodules and aggregates was unlike the pattern of massive thymic infiltration seen in 7 previously reported cases of thymic Langerhans cell histiocytosis in childhood. This difference led us to consider whether these aggregates might be common in the thymus but overlooked in thymus glands removed incidental to cardiac surgery. We examined histologic material from 22 sequential thymectomy specimens removed during cardiac surgery from infants and children. None (0/22) had cohesive aggregates of Langerhans cells, as were seen in the index patient's thymus. Our patient's small thymic nodules resemble more closely a pattern found in adult patients with myasthenia gravis who have been incidentally shown to have Langerhans cell histiocytosis.

Low-grade osteosarcoma of the jaw.

We describe a case of low-grade osteosarcoma of the jaw. The patient is a 25-year-old woman who presented with large, nontender, slowly progressive, expansile left mandibular mass. X-ray showed a predominantly hypodense mass with erosive growth pattern affecting the angle, posterior body, and ramus of the left mandible. The patient underwent left hemimandibulectomy. The tumor was a white-tan, well-circumscribed, multinodular, firm mass that measure 7.0 cm. Microscopically, the tumor was composed of bland spindle cells, with minimal cellular atypia, absent mitotic figures, very focal osteoid formation with extensive bone destruction, and soft tissue infiltration. Immunhistochemical stains for a large panel of antibodies were noncontributory. At present the patient is alive and well 7 months after surgery.

Pseudoangiomatous stromal hyperplasia of the breast.

Pseudoangiomatous stromal hyperplasia is a benign proliferative lesion of the mammary stroma that rarely presents as a localized mass. We describe the clinical, radiologic, cytologic, and histologic features of a case of pseudoangiomatous stromal hyperplasia that presented as a rapidly growing breast lesion in a 36-year-old woman.