Two tumors with combined features of bronchiolar adenoma/ciliated muconodular papillary tumor and sclerosing pneumocytoma.

OBJECTIVES: Bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT) and sclerosing pneumocytoma (SP) are both rare and morphologically unique peripheral lung tumors with indolent behavior. These tumors have not been previously described as showing overlapping morphologic features and are generally genetically distinct. METHODS: Two cases were recently encountered that show hybrid morphologic features between BA/CMPT and SP, and the morphology and immunophenotype are described in detail. RESULTS: Both cases showed interstitial round cells typical of SP (TTF1+, EMA+), as well as areas more typical of BA/CMPT. One case showed BRAFV600E expression in the BA/CMPT areas but not in the SP-like cells. CONCLUSIONS: Although it is possible that these cases represent collision tumors or are examples of unusual metaplastic epithelial changes in SP, they also raise the possibility that these 2 entities could occasionally coexist in true hybrid tumors.

Validation of Linear Range HER2/Estrogen Receptor/Progesterone Receptor IHControls for Daily Quality Assurance.

OBJECTIVES: To evaluate a new US Food and Drug Administration (FDA)-cleared immunohistochemistry (IHC) control (IHControls [Boston Cell Standards]) comprising peptide epitopes for HER2, estrogen receptor (ER), and progesterone receptor (PR) attached to cell-sized microspheres and to compare its performance against conventional tissue controls. METHODS: IHControls and tissue/cell line controls for HER2, ER, and PR were compared side by side daily at 5 clinical IHC laboratories for 1 to 2 months. Separately, the sensitivity of the 2 types of controls was evaluated in simulated IHC assay failure experiments by diluting the primary antibody. Additional evaluations included lot-to-lot manufacturing reproducibility of 3 independent lots and specificity against 26 antigenically irrelevant IHC stains. RESULTS: Side-by-side testing revealed a 99.6% concordance between IHControls and tissue controls across 5 IHC laboratories and 766 individual evaluations. Three discordant quality control events were the result of operator error. Simulated assay failure data showed that both IHControls and tissue controls are similarly capable of detecting IHC staining errors. Manufacturing reproducibility of IHControls showed less than 10% variability (coefficient of variation). No cross-reactions were detected from 26 antigenically irrelevant IHC stains. CONCLUSIONS: IHControls, the first FDA-cleared IHC controls, can sensitively and accurately detect IHC assay problems, similar to tissue controls.

A Molecular and Cytogenetic Update on Non-Small Cell Lung Carcinoma.

Lung cancer is one of the leading causes of cancer-related death worldwide. Among patients with lung cancer, approximately 85% have non-small cell lung carcinoma (NSCLC). The discovery of oncogenic driver mutations in NSCLC opened new personalized treatment options. Several methods that can identify these biomarkers are used routinely in a clinical setting to stratify patients for targeted therapy. In this review, we summarize the most clinically relevant driver genes, discuss the advantages and limitations of current clinical detection methods, and highlight the benefits of personalized treatment over standard chemotherapy.

Fatal Cokeromyces recurvatus pneumonia: report of a case highlighting the potential for histopathologic misdiagnosis as coccidioides.

Cokeromyces recurvatus is a dimorphic zygomycete with histologic morphology similar to Coccidioides immitis. A 66-year-old man who was status-post bone marrow transplantation for chronic myelogenous leukemia was hospitalized with new onset rash, nausea, and vomiting and subsequently expired. A sputum culture collected on the day of death revealed heavy growth of C. recurvatus 6 days after collection. At autopsy, microscopic examination of the lungs revealed numerous thick-walled, nonbudding spherules ranging in size from 40 to 80 µm. Initial immunohistochemical staining of the formalin-fixed lung tissue was positive for Coccidioides. Additional immunoperoxidase staining revealed the organisms were consistent with a zygomycete fungus, compatible with C. recurvatus infection. Polymerase chain reaction using panfungal primers was attempted on the formalin-fixed tissue but was inconclusive. This case highlights the potential for misdiagnosing Cokeromyces as Coccidioides when the diagnosis is based on histology and immunohistochemical staining.

Use of therapeutic plasma exchange in the management of acute hemorrhagic leukoencephalitis: a case report and review of the literature.

BACKGROUND: Acute hemorrhagic leukoencephalitis (AHLE) is a rare, fatal, central nervous demyelinating disease characterized by a rapid fulminant clinical course. Successful management requires early diagnosis, aggressive management of cerebral edema, and immunosuppression. Therapeutic plasma exchange (TPE) is infrequently used and commences after initial management fails. CASE REPORT: A 31-year-old man presented with right arm weakness, whose symptoms rapidly progressed to hemiplegia and aphasia. The patient was initially managed with glucocorticosteroids. Decompressive craniotomy and brain biopsies were performed when his intracranial pressure increased. Brain biopsy findings were consistent with AHLE. Mycoplasma pneumonia immunoglobulin G and immunoglobulin M serologies revealed recent infection. Despite surgical and medical management, he decompensated on Day 11, and TPE was initiated. The patient received a total of 10 TPE treatments. On the fourth day of TPE treatment, he was extubated. Twenty-one days after TPE began, he was ambulating with near normal muscle strength and was discharged. Four months after initial presentation, the patient has normal strength and is working full-time. CONCLUSIONS: AHLE has a fulminant course requiring accurate and rapid diagnosis. Successful therapy requires aggressive management of intracranial pressure and immunosuppression. Two other reports of AHLE document successful management with TPE. Each of these patients survived with minimal neurologic impairments. Given the likely immune-mediated nature of this disease, combined treatment of steroids, surgery, and TPE may lead to shorter hospital stays and improved neurologic outcomes. Clinical studies are needed to further study the effect of TPE on neurologic outcome in AHLE.

Endoscopic ultrasound-guided fine needle aspiration diagnosis of metastatic sex cord tumor with annular tubules: a case report.

The cytologic findings of a paratracheal metastasis from a malignant sex cord tumor with annular tubules (SCTATs) diagnosed by endoscopic ultrasound guided fine needle aspiration are described. Cytologic features of SCTATs include the presence of highly cellular aspirates forming simple and complex rosette-like structures around central rounded hyaline material, small nucleoli, and prominent nuclear grooves. These cytologic findings are clearly distinct from the poorly formed rosette-like structures of granulosa-cell tumors and are reminiscent of the low-power appearance of the cribriform variant of adenoid cystic carcinoma. The fine needle aspiration cytologic features of only two other cases have been previously described and, to the best of our knowledge, this is the first case reporting the cytologic diagnosis of a distant metastasis of a SCTATs by endoscopic ultrasound-guided fine needle aspiration. In this case, the distinctive and characteristic cytologic features have allowed the proper diagnosis of a distant metastasis of SCTATs.

The economic impacts of Oklahoma's Family Medicine residency programs.

The enactment of Medicare and Medicaid created a new demand for medical services in Oklahoma, particularly in rural areas. The state of Oklahoma responded by creating The Oklahoma Physician Manpower Training Commission in 1975. The overall purpose of the Commission was to increase the number of primary care physicians and influence distribution into non-metro areas. This analysis concerns the public policy value of this ongoing program. The PMTC has provided resident stipend funding to each of Oklahoma's publicly funded Family Medicine residency programs. Since 1975, the PMTC has provided over 139 million dollars in resident stipend funding and support; and there have been 749 program graduates with 431 practicing in Oklahoma. This model calculates that the Oklahoma-based physicians have created a cumulative 3.7 billion dollars of economic impact on the state; and conservatively estimates that only 10% of the practice decisions/locations were influenced by the PMTC. This creates an estimated return of 370 million dollars on an "investment" of 139 million dollars. Additionally the model demonstrates that the current cohort of physicians is annually responsible for 15,530 jobs and an associated payroll of 428 million dollars.

State public policy: the impacts of Oklahoma's physician incentive programs.

The enactment of Medicare and Medicaid created a sudden and significant increase in demand for physician services in Oklahoma. As a response, the Oklahoma Legislature established the Physician Manpower Training Commission in 1975. The intent was to provide incentives for graduating physicians to remain in Oklahoma, especially in rural areas. This analysis examines the retention rates experienced during the 25-year period of 1976-2001. It is observed that 82% of program physicians are currently practicing in Oklahoma. This retention proportion compares to only 36% for National Health Service Corps physicians who were obligated to practice in Oklahoma. Additionally, Oklahoma has experienced a 67% retention proportion in rural areas. During this period, 633 physicians have received an estimated dollar 19 million in loans and scholarships. This is an average of dollar 30,000 per recipient. In return, each of these physicians will create 34 jobs and almost dollar 1 million of annual income.