The Need for Laboratory Medicine in the Undergraduate Medical Education Curriculum: A White Paper from the Association of Pathology Chairs.

Considering laboratory results are used to make medical decisions, a fundamental understanding of laboratory medicine is paramount to enhance patient care, optimize health care cost containment, and prevent legal repercussions. With increasing laboratory testing complexity, this education is needed now more than ever. This article is a call to action to have medical schools adequately incorporate practical laboratory medicine content into their undergraduate medical education (UME) curricula. The authors discuss the definition of laboratory medicine, what it encompasses, who uses it and why it matters, and propose that a core laboratory medicine curriculum is a necessary part of UME.

Recent challenges in infectious diseases. Biological pathogens as weapons and emerging endemic threats.

This article reviews emerging and re-emerging infectious diseases and provides insights regarding the evolution of our understanding of natural diseases and how that knowledge impacts the development of plans and methods for defending against the deliberate use of biological agents. Also discussed are forensic and legal issues for the pathologist concerning agents of biological terrorism and biological warfare, the concept of chain of custody, transport, storage, and biosafety levels. It defines the importance of the pathologist in managing the threat posed by biological weapons.

The vomeronasal organ: an objective anatomic analysis of its prevalence.

The function and location of the vomeronasal organ in humans remains poorly understood. Indeed, there has been considerable controversy as to whether it even exists. Until now, there has been no published report of its prevalence or location as ascertained by the most widely accepted visual operative instrument in sinonasal surgery: the rigid nasal endoscope. In this study, multiple observers used the nasal endoscope to determine the prevalence and character of the vomeronasal organ in humans. We performed nasal endoscopy on 22 cadaver heads and 78 live humans; we also biopsied cadaver specimens to histologically confirm the endoscopic diagnosis. We found evidence of this organ in 13 of the 22 cadavers (59.1%) and in 22 of the 78 patients (28.2%). Many nasal surgeons are unaware of this organ and its potential physiologic significance. It is our hope that by recognizing its prevalence and location, nasal surgeons will be more likely to identify and possibly preserve this mysterious organ until its function is more clearly understood.

Extralobar sequestration with frequently associated congenital cystic adenomatoid malformation, type 2: report of 50 cases.

Extralobar pulmonary sequestration (ELS) represents a mass of pulmonary parenchyma separate from the normal lung. The coexistence of congenital cystic adenomatoid malformation (CCAM) in ELS has been reported. To define this association, the clinical, gross, and histologic features of 50 ELS cases were analyzed. The age at diagnosis varied from birth to 65 years with 24% of cases diagnosed prenatally and 61% (23/38) diagnosed within the first 3 months of life. Fifty-two percent of cases were in females and 48% in males. Forty-eight percent of ELS(s) were located in the left hemithorax, 20% in the right hemithorax, 8% in the anterior mediastinum, 6% in the posterior mediastinum, and 18% beneath the diaphragm. The blood supply to the sequestration in 77% of cases was directly from the aorta. Grossly, the lung, though hypoplastic in some cases, was otherwise unremarkable. Fifty percent (23/46) of ELS cases were associated with a coexistent CCAM. In contrast to the series as a whole, 92% (11/12) of the ELS/CCAM cases, excluding those prenatally diagnosed, were diagnosed within the first 3 months and 57% occurred in females. ELS/CCAM lesions, while randomly distributed, were more frequently seen on the left side. Gross features of the ELS/CCAM cases were similar to those cases with ELS alone. All CCAM cases had a type 2 pattern on histologic examination with 48% of those cases also displaying rhabdomyomatous dysgenesis. Our findings indicate that the occurrence of CCAM in ELS is more frequent than reported in the literature and differs in presentation from ELS cases not associated with CCAM.

An approach to handling pediatric thyroid and adrenal tumors excluding neuroblastoma.

Thyroid and adrenal tumors, excluding neuroblastoma, are infrequent in children. Because of the problems involved in applying diagnostic and prognostic criteria developed for adult tumors to pediatric tumors, proper diagnosis of thyroid and adrenal tumors in pediatric patients and proper patient management require close collaboration on the part of clinicians, surgeons, and surgical pathologists. In view of that fact, an approach to handling thyroid and adrenal tumors is presented. Special attention is paid to the following aspects of managing both types of tumors: procedure, fine-needle aspiration, intraoperative consultation (frozen sections), gross examination, histologic examination, special studies, diagnosis, and prognostic features.

Pulmonary inflammatory pseudotumor: radiologic features.

PURPOSE: To define the radiologic features of pulmonary inflammatory pseudotumor. MATERIALS AND METHODS: Between 1966 and 1994, 61 cases of pulmonary inflammatory pseudotumor involved 36 male and 25 female patients (age range, 17 months to 61 years; mean, 28 years). Clinical presentation, pathologic features, and radiologic findings were noted. RESULTS: At radiography, 52 patients had solitary peripheral nodules or masses, and extraparenchymal involvement--including hilar, mediastinal, and airway invasion--was found in 11. At computed tomography, 12 lesions were of heterogeneous attenuation and five, homogeneous. At T1-weighted magnetic resonance imaging, five lesions had intermediate signal intensity; of two lesions studied with T2-weighted imaging, two had high signal intensity; and the one lesion studied with gadolinium-enhanced imaging had diffuse enhancement. CONCLUSION: Pulmonary inflammatory pseudotumor was typically a solitary, peripheral, sharply circumscribed mass with an anatomic bias for the lower lobes. Local invasion and primary involvement of the mediastinum and hilar structures were unusual manifestations.

Effects of fixative and fixation time on the extraction and polymerase chain reaction amplification of RNA from paraffin-embedded tissue. Comparison of two housekeeping gene mRNA controls.

A number of reports have indicated that RNA recovered from paraffin-embedded tissue can be used as a substrate in the polymerase chain reaction (PCR). Although it is established that RNA in paraffin-embedded tissue undergoes significant degradation, the specific contributions of different fixatives and fixation times to this degradation are not known. Mouse splenic tissue was harvested and fixed immediately for 2, 8, or 24 h in either formalin, Omnifix II, or Carnoy's fixative and then processed and embedded in paraffin. RNA was extracted from deparaffinized cubes of tissue using an adaptation of the technique described by Chomczynski and Sacchi. RNA was reverse transcribed using a random hexamer primed reaction. PCR amplification for cDNAs of the housekeeping genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and hypoxanthine phosphoribosyltransferase (HPRT) mRNAs was then performed. Although GAPDH amplification is used routinely on fresh and frozen tissues, we show that the presence of DNA contamination in the RNA preparations limits its usefulness in paraffin-embedded tissue. Amplifiable HPRT mRNA sequences were detected in nine of 12 samples fixed in Omnifix II, in four of 12 samples fixed in Carnoy's fixative, and in none of 12 formalin-fixed samples. Because of primer selection to preclude amplification of genomic HPRT, DNA contamination is not an issue when HPRT is amplified. Thus, HPRT represents the control system of choice for the evaluation of RNA in PET. The techniques described provide a rapid, uniform, and reproducible method of obtaining RNA from PET for molecular analysis, but they indicate limited utility for retrospective analysis of archival tissues.

Triploid abortus presenting as an ectopic pregnancy.

In this article we present a case of an ectopic gestation having morphologic features of a partial hydatidiform mole and demonstrating triploidy by flow cytometry in a patient presenting at 9 weeks' gestation. We include brief comments on partial hydatidiform mole.

Diagnostic considerations in molar gestations.

Hydatidiform moles (HMs) are classified as partial or complete based on a combination of gross, histologic, and karyotypic features. Adherence to strict and reproducible diagnostic criteria is needed to ensure accurate diagnosis and minimize interpathologist variability. Using the kappa statistic as a measure of agreement, the morphologic, flow cytometric, and clinical features of 80 cases of HM or suspected HM were analyzed sequentially by three pathologists to evaluate intrapathologist and interpathologist variability. Poor interpathologist agreement was obtained when histology alone was used for diagnosis. The combination of gross morphology and histology resulted in poor to good agreement. Good interpathologist agreement was obtained, however, when objective data (DNA content determined by flow cytometry) were included in the analysis. Our data indicate that pathologist concordance is maximized when the diagnosis is based on a combination of morphology and DNA content.

Oropharyngeal teratomas: a clinicopathologic study of four cases.

Oropharyngeal teratomas (OPT) represent an uncommon congenital tumor with significant morbidity and mortality. Optimal management requires prenatal diagnosis. The clinicopathologic features of four OPT (one stillbirth, two livebirths, and one therapeutic abortion) are reviewed and compared with cases previously reported in the literature. Diagnosis, management, clinical outcome, and the natural history of the entity are discussed.

Hepatoblastoma: the prognostic significance of histologic type.

The clinicopathologic features of 105 hepatoblastomas accessioned to the Armed Forces Institute of Pathology between 1967 and 1987 were reviewed. DNA content was analyzed by flow cytometry. A multivariate analysis using the Cox proportional hazards model was performed to evaluate the effect of stage, histologic type, and DNA content on the prognosis for survival. The relative risks of death for a given stage compared to the other stages combined were 0.1637, 0.5672, 2.8742, and 3.5148 for stages I-IV, respectively. The relative risk of death for a given histologic type adjusted for age, sex, and stage compared to the other types was 1.0739 (p = .8850) for the fetal pattern, 1.7409 (p = .1662) for the embryonal pattern, 0.5292 (p = .0754) for the mixed pattern, 1.1980 (p = .7729) for the macrotrabecular pattern, and 3.7096 (p = .1061) for the small-cell undifferentiated pattern. Of 19 hepatoblastomas analyzed for DNA content, 5 were DNA diploid and 11 were DNA aneuploid; 3 could not be classified. The stage of disease at presentation proved to be a significant prognostic factor, whereas histologic type and DNA content did not have a significant effect.

Kaposi's sarcoma of the bone marrow.

We report a case of Kaposi's sarcoma of the bone marrow presenting as a myelophthisic anemia with bone marrow necrosis. The patient did not fit into any of the current clinical patterns described for Kaposi's sarcoma. This case illustrates the need for including Kaposi's sarcoma in the differential diagnosis of myelophthisic anemia.

Malignant fibrous histiocytoma of the liver--a case report.

A case of primary malignant fibrous histiocytoma of the liver studied by light and electron microscopy and confirmed at autopsy is presented. Malignant fibrous histiocytoma, the most common adult soft tissue sarcoma, has been reported in most organs but to date has not been described as a primary liver tumor.

Atrophy of the zona fasciculata in the adrenal cortex of thyroparathyroidectomized rats: a quantitative study.

Atrophy of the adrenal gland induced by thyroparathyroidectomy (TPX) is attributable primarily to narrowing of the zona fasciculata. But absolute volumes of the adrenal gland and zona fasciculata, not the zona glomerulosa and zona reticularis, were decreased significantly 7 weeks after TPX. Changes consistent with atrophy were also seen in the zona fasciculata by electron microscopy. A slight decrease in volume of cytoplasm in cells of the zona fasciculata was evident 2 weeks after TPX as shown by quantitative stereological techniques. Seven weeks after TPX, there was a significant decrease in average cytoplasmic volume as well as mitochondrial volume and surface density of mitochondrial membranes. A decrease in total volume of the zona fasciculata, as well as volume per cell of mitochondria, correlates directly with decreased production of corticosterone in response to stress in TPX rats. Parathyroidectomy (PX) had no effect on the volume of the adrenal gland, on the volume of the individual cortical zones, or on the volume per cell of cytoplasm or mitochondria; these observations indicate that changes in TPX rats are due primarily to ablation of the thyroid gland.

Thyroparathyroidectomy increases the activity of catalase in the adrenal gland of the rat. A structural and functional study.

At four weeks after thyroparathyroidectomy the activity of catalase in adrenal homogenates was significantly greater (2.95 +/- 0.06 mumoles 0(2)/min/mg protein) than that of controls (2.17 +/- 0.09 mumoles 0(2)/min/mg protein). Increased activity of catalase is related directly to more numerous peroxisomes in cortical cells in the zona fasciculata-zona reticularis of thyroparathyroidectomized rats. The absolute and relative volumes of adrenal gland and zona fasciculata were reduced significantly which is directly correlated with increased peroxisomal activity. A hormonally mediated mechanism reflecting alteration in ACTH, growth hormones and thyroid hormones may mediate adrenocortical atrophy and in turn increase in activity of catalase.

Parathyroidectomy ameliorates vascular lesions induced by deoxycorticosterone in the rat.

The systolic blood pressures of rats that underwent parathyroidectomies and uninephrectomies reached hypertensive levels after implantation of deoxycorticosterone (DOC) pellets and were compared to those in rats with intact parathyroids bearing 20-mg or 50-mg pellets of DOC. Parathyroidectomy, however, ameliorated the incidence and severity of cardiac and renal lesions induced by DOC. The beneficial effect of parathyroidectomy on vascular lesions may well be attributable at least in part to a reduced level of calcium in the serum or to the absence of parathyroid hormone, which is involved directly in the regulation of calcium transport and influx into the cell. Parathyroidectomy significantly reduced the compensatory renal hypertrophy and splenomegaly induced by DOC, although cardiac hypertrophy and hepatomegaly induced by DOC were not affected by parathyroidectomy.

Adrenal regeneration hypertension prevented by thyroidectomy: a quantitative ultrastructural study of the regenerating adrenal cortex.

Thyroparathyroidectomy (TPX) prevents adrenal regeneration hypertension (ARH) in female rats and concomitantly inhibits regeneration of the adrenal cortex. Removal of the thyroid gland plays the major role in preventing ARH inasmuch as parathyroidectomized adrenal-enucleated (PX-AE) rats became hypertensive, whereas thyroparathyroidectomized adrenal-enucleated rats (TPX-AE + PT) did not. Inhibition of adrenocortical regneration by TPX is reflected by a significant decrease in adrenal weight, volume of cortical parenchymal tissue per gland, and average cell volume at three weeks, compared with the regenerating adrenal gland in adrenal-enucleated thyroid-parathyroid-intact (AE) rats. Mitochondria in TPX-AE rats resembled closely those from zona fasciculata cells of a normal adrenal gland; stereologic techniques for electron microscopic examination confirmed that mitochondrial volume/cell and surface area of total mitochondrial membranes/cell (outer/inner membranes plus cristae) of adrenocortical cells from TPX-AE rats did not differ significantly from those of AE animals. The surface area of mitochondrial cristae of TPX-AE rats, however, was significantly greater than that of AE rats, whereas the surface area of the inner/outer mitochondrial membrane of the TPX-AE group was decreased significantly as compared with that of the AE group. The diameter of mitochondria in TPX-AE rats was larger than in the AE group, although the number of mitochondria/cell was significantly less in TPX-AE rats than in AE rats. Although TPX had no significant effect on the levels of DOC or corticosterone in the serum of quiescent AE rats as compared with TPX-AE rats, the rise in DOC in the serum after ether stress was blunted in the TPX-AE group as compared with that in the AE group. The rise in corticosterone in the TPX-AE group was comparable to that of the AE animals. Thus, partial inhibition of adrenal regeneration in TPX-AE rats in combination with a blunted rise in DOC levels in response to stress may well contribute to the prevention of ARH.

Effect of thyroparathyroidectomy (TPX) on the zona reticularis: a quantitative ultrastructural study.

Atrophy of zona reticularis cells was observed two weeks after surgical thyroparathyroidectomy (TPX). Quantitative morphological techniques for electron microscopy showed significant decreases in the volume of cytoplasm, nucleus, mitochondria, smooth endoplasmic reticulum and lipid droplets in the zona reticularis of TPX rats. In addition, many mitochnodria contained lipid droplets, some of which occupied virtually the entire matrix of mitochondria. The volume per cell of mitochondria with these inclusions increased significantly after TPX. The lipid droplets may well arise from cytoplasmic droplets by increased transport or reduced metabolism of cholesterol, or by direct incorporation of droplets into the mitochondrial matrix. The serum corticosterone level of TPX rats sacrificed under quiescent conditions did not differ significantly from that of controls. Hypothyroidism induced a significant increase in the volume of peroxisomes per cell in TPX animals which may be related to changes in lipid metabolism or transport.