Histopathology of the alarm reaction in small odontocetes.

Pathological changes in the organs and tissues of beach-stranded, net-caught or captive small odontocete cetaceans (whales and dolphins) are reported. These changes include contraction band necrosis of cardiac and smooth muscles, smooth muscle spasm, ischemic injury to the intestinal mucosa (especially the mucosa of the small intestine) and acute tubular necrosis (ATN) of the proximal tubules of the nephron. Spastic contraction of terminal bronchiolar muscular sphincters was also observed. The changes are consistent with multi-systemic injury caused by massive release of endogenous catecholamines or vasospasm leading to ischemic injury, followed by reperfusion and reperfusion injury. The histopathological findings suggest that the reflex response of an odontocete to any major perceived threat (the "alarm reaction") is to activate the physiological adaptations to diving or escape to an extreme or pathological level, resulting, if greatly prolonged, in widespread ischemic injury to tissues. These observations may explain why these species die abruptly from handling or transportation and why the mortality of highly stressed beach-stranded animals is very high.

Histological, immunohistochemical and pathological features of the pituitary gland of odontocete cetaceans from the Western gulf of Mexico.

Pituitary glands were recovered from dolphins and small whales found stranded along the Texas coast of the Gulf of Mexico over a 15-year period (1991-2006). One hundred animals of 14 species were found to be suitable for inclusion in this study. Of these, 72 were Atlantic bottlenose dolphins (Tursiops truncatus). Other species included were the melon-headed whale (Peponocephala electra), spinner dolphin (Stenella longirostris), striped dolphin (Stenella coeruleoalba), pantropical spotted dolphin (Stenella attenuata), pygmy sperm whale (Kogia breviceps), dwarf sperm whale (Kogia sima), Risso's dolphin (Grampus griseus), the short finned pilot whale (Globicephala macrorhyncha), false killer whale (Pseudorca crassidens), Fraser's dolphin (Lagenorhynchus hosei), rough-tooth dolphin (Steno bredanensis), Gervais's beaked whale (Mesoplodon europaeus) and an infant sperm whale (Physeter catodon). The pituitary weights in T. truncatus ranged from 0.69 g in a 109-cm long neonate to 3.44 g in a large (277 cm) male. More typical weights were in the range of 0.95-2.35 g (mean=1.65+/-0.70 g) The cetacean pituitary consisted of two distinct parts, the adenohypophysis and the neurohypophysis, which were separated by a thin fibrous membrane in all species examined, in contrast to terrestrial mammals in which the parts are apposed and joined through a pars intermedia. Cell types were identified with conventional stains and immunohistochemistry. Cells positive for adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, melanocyte stimulating hormone, luteinizing hormone and prolactin were identified with appropriate antibodies. Lesions, which were few, included one pituicytoma of the pars nervosa and a squamous cyst in T. truncatus, and colloid cysts in several species. Nodular aggregates of single cell types were common, probably representing a physiological variant.

The thyroid gland in bottlenose dolphins (Tursiops truncatus) from the Texas coast of the Gulf of Mexico: normal structure and pathological changes.

Fresh thyroid glands (n=60) from Atlantic bottlenose dolphins that died after stranding along the Texas coast between 1991 and 2005 were examined. Organ weight ranged from 11 g in a neonate (length 109 cm) to 58 g in a large (249 cm) male. More typical weights were 25-45 g (mean=30.6 g). Glands tended to be larger in pregnant and lactating females (mean 37.4 g; n=5) than in non-pregnant animals of comparable size. In infancy, the gland tended to be compact, relatively homogeneous, and sometimes partly lobular, but with advancing age it became more lobular, the lobules being defined by fibrous bands. In one 8-year-old female (233 cm), and in a large male (295 cm) aged>25 years the gland was represented by a cluster of lobules. Lobulation was not necessarily accompanied by increased weight, distinguishing it from hyperplasia. With age, variation in follicle size and colloid density tended to increase. Two animals (3%) had adenomas and five (8%) had discrete hyperplastic nodules, not to be confused with lobulation. Five (8%) had macroscopically identifiable colloid-filled cysts (1-4 mm in diameter). Nine animals (15%) had squamous cysts (4-15 mm) containing creamy white fluid. Other abnormalities included patchy or diffuse interstitial fibrosis (six cases, 10%) amyloidosis (two cases), thyroiditis (one case) and vasculitis (one case). No malignant neoplasms were found. Cells presumed to be C cells (light cells, parafollicular cells) were identified immunohistochemically with synaptophysin antibody.

Morphological changes in the Atlantic bottlenose dolphin (Tursiops truncatus) adrenal gland associated with chronic stress.

Beach-stranded Atlantic bottlenose dolphins (n=68) were categorized as either "acutely stressed" (if they died from net entanglement, boat strike, or acute infection; 31 animals) or "chronically stressed" (if they suffered from or died as a result of long-term disease or debilitating injury; 37 animals). No significant differences in mass between the right and left adrenal glands were found within each category. However, the average gland mass (AGM), based on the right and left glands together, was 5.2g for acutely stressed animals and 11.01 g for chronically stressed animals (P<0.001). Significant differences were also found, in terms of the ratio of cross-sectional areas of the cortex to medulla, between acutely stressed (ratio 1.22) and chronically stressed (ratio 1.63) animals (P=0.027). Adrenal glands of acutely stressed animals consisted of 48% cortex, 41% medulla, and 11% other tissue elements (connective tissue, blood vessels and gland capsule), whereas the corresponding figures for chronically stressed animals were 53%, 36%, and 11%. The mean estimated mass values for cortex, medulla and other tissue were, for acutely stressed animals, 2.36, 1.9, and 0.54, respectively, whereas for chronically stressed animals the corresponding figures were 6.06, 4.04, and 1.29 (P<0.001 for each of the three comparisons). Overstaining with haematoxylin (HEM) and immunohistochemical labelling (IHC) of the enzyme phenylethanolamine N-methyl transferase (which converts norepinephrine to epinephrine) were used to determine the percentage of epinephrine-producing cells in relation to the overall cross-sectional area of the adrenal gland. The percentage values in acutely as compared with chronically stressed dolphins were 6.7% and 15.93%, respectively (P=0.021). The results therefore suggest that in bottlenose dolphins chronic stress results in increases in (1) adrenal mass, (2) cortex to medulla ratio, and (3) epinephrine-producing cells within the medulla, giving rise to an increase in the thickness of the medullary band.

Transitional cell carcinoma with rhabdoid features.

We discuss the light-microscopic, immunohistochemical, electron-microscopic, and flow cytometric analysis in a case of invasive transitional cell carcinoma of the renal pelvis with rhabdoid features and glandular metaplasia. This tumor demonstrated in situ rhabdoid transformation of the transitional epithelium, which has not been described before. Electron-microscopic examination of the rhabdoid cells revealed whorled aggregates of intermediate filaments. There was also evidence of mucin-filled intracellular lumina on light and electron microscopy in both in situ and invasive components of the tumor. Our findings lend support to the view that tumors with "rhabdoid" features in adults and perhaps some children represent a heterogeneous group of neoplasms, some of which may just be unusual morphologic variants of a transitional cell carcinoma, in contrast to the distinct clinicopathologic entity of childhood renal rhabdoid tumors.

Recurring phyllodes tumor in aberrant breast tissue of the vulva.

A 20-year-old nulligravida woman presented with bilateral cystic nodules of the vulva, diagnosed after simple excision as benign phyllodes tumor. Breast tissue, which also displayed fibrocystic changes, was also recognized. Follow-up at 2 months revealed no evidence of disease; however, 8 months after surgery she returned with a new mass in the vulva. This was excised and found to be recurrent phyllodes tumor. Although somewhat more cellular than the first lesions, it also was deemed to be benign based on histological features supported by flow cytometric DNA studies.

Primary intratracheal neurilemoma.

We report a case in a 38-year-old white woman of a benign primary intratracheal neurilemoma that recurred 12 years after an initial endoscopic excision. Of the 12 intratracheal neurilemomas that have previously been reported, all occurred in white persons in an age range of 6 to 71 years and most were located in the lower trachea and produced symptoms of cough and wheezing.

Increased collateral arterial and venous endothelial cell turnover after renal artery stenosis in the dog.

Renal artery stenosis was induced in dogs and collateral arterial formation assessed by serial angiography and histology. Endothelial cell turnover was estimated by radioautography in five normal and five collateral-forming kidneys 18-39 days following stenosis with tritiated thymidine. Normal arterial endothelial labeling was 0.1% with a highly significant (p less than 0.0005), 55-fold increase in endothelial labeling in arterial collateral vessels. A smaller but statistically significant increase in the labeling index was also found in endothelial cells of the renal vein, from a normal of 0.065% to 0.4% (p less than 0.005). An excellent correlation was found between endothelial cell labeling in small arteries and the renal veins (r = 0.97; p less than 0.01). A marked increase in epithelial cell labeling of the ureters draining the stenotic kidneys was also evident (p less than 0.005). Thus, collateral vessel development is characterized by active DNA synthesis in cellular elements, and a humoral factor is implicated in the vascular response.

High aerobic capacities in the skeletal muscles of pinnipeds: adaptations to diving hypoxia.

The objective was to assess the aerobic capacity of skeletal muscles in pinnipeds. Samples of swimming and nonswimming muscles were collected from Steller sea lions (Eumetopias jubatus, n = 27), Northern fur seals (Callorhinus ursinus, n = 5), and harbor seals (Phoca vitulina, n = 37) by using a needle biopsy technique. Samples were either immediately fixed in 2% glutaraldehyde or frozen in liquid nitrogen. The volume density of mitochondria, myoglobin concentration, citrate synthase activity, and beta-hydroxyacyl-CoA dehydrogenase was determined for all samples. The swimming muscles of seals had an average total mitochondrial volume density per volume of fiber of 9.7%. The swimming muscles of sea lions and fur seals had average mitochondrial volume densities of 6.2 and 8.8%, respectively. These values were 1.7- to 2.0-fold greater than in the nonswimming muscles. Myoglobin concentration, citrate synthase activity, and beta-hydroxyacyl-CoA dehydrogenase were 1.1- to 2. 3-fold greater in the swimming vs. nonswimming muscles. The swimming muscles of pinnipeds appear to be adapted for aerobic lipid metabolism under the hypoxic conditions that occur during diving.

Invasive verrucous carcinoma of urinary bladder treated by irradiation.

A case of inoperable, invasive verrucous carcinoma of the urinary bladder treated by irradiation is presented. The incidence of anaplastic transformation of verrucous carcinoma after irradiation is lower and the coincidence of verrucous carcinoma and well-differentiated squamous carcinoma higher than is generally recognized. Radiation should be considered in inoperable cases. The pertinent literature is reviewed.

Mechanism of healing of the human prostatic urethra following thermal injury.

OBJECTIVES: To characterize histopathologically the healing response of the prostatic urethra after laser thermal coagulation and standard transurethral resection of the prostate (TURP). METHODS: The study included 31 patients who underwent radical prostatectomy because of malignancy. Twenty-two (first group) had laser radiation either at the time of surgery (18 patients) or from 1 to 12 weeks prior to prostatectomy (4 patients). Nine patients (second group) had TURP from 6 to 96 weeks prior to prostatectomy. RESULTS: Coagulation necrosis followed by sloughing was observed during the first 10 weeks after laser radiation. After the first 10 weeks, the healing response was otherwise stereotypical and comparable for both groups of patients. Re-epithelialization was prominent and resulted from migration of proliferating epithelial cells from the remaining acinar and ductal epithelium. Squamous metaplasia was conspicuous and present indefinitely. Development of inflammatory reaction followed by granulation tissue and well-organized fibroblastic stroma were sequentially recognized, but less prominent. Complete re-epithelialization and wound sealing was not observed before the first 12 weeks of healing. CONCLUSIONS: Our study suggests that laser thermal coagulation and TURP are partial-thickness injuries. Because of the abundant germinal epithelium in the remaining prostatic glands and ducts, the healing response of the prostatic urethra is relatively unimpeded and free of contractures, analogous to second-degree skin burns.

Thermocoagulation effect of diode laser radiation in the human prostate: acute and chronic study.

OBJECTIVES: To evaluate the safety and efficacy of low-power slow-heating diode laser-induced photocoagulation of prostatic tissue for treatment of benign prostatic hyperplasia, we conducted a series of acute and chronic studies using a diode laser (810 nm) to irradiate human prostate. METHODS: The study included 6 patients undergoing radical prostatectomy because of malignancy. Laser radiation to the prostate was given transurethrally, in a noncontact mode, at the time of the procedure in 2 patients (acute group): 10 W for 300 seconds on the right side of the prostate and 15 W for 180 seconds on the left. In the remaining 4 patients (chronic group), laser radiation was given at 1, 7, 10, and 12 weeks prior to the prostatectomy. RESULTS: In the acute group the average depth of coagulation was 8.5 and 9.0 mm for the laser regimens of 15 W for 180 seconds and the 10 W for 300 seconds, respectively. In the chronic group, the average depth of coagulation was 8.9 mm for both laser regimens studied. In the acute group, there was an ill-defined hemorrhagic ring at the periphery of the lesion. At 1 week, an intact necrotic coagulum was present. At 7 weeks, some of the coagulated tissue had already sloughed off. Longer follow-up at 10 and 12 weeks demonstrated formation of a well-defined cavity with mostly re-epithelialized surface. CONCLUSIONS: Our findings suggest that noncontact diode laser (810 nm) irradiation can induce in the human prostate significant coagulation necrosis followed by sloughing of tissue and cavitation of the prostatic urethra.

Morphology of complex lymphoepithelial organs of the anal canal ("anal tonsil") in the bottlenose dolphin, Tursiops truncatus.

A complex of lymphoepithelial organs, the "anal tonsils," is a consistent structure in the anal canal of the bottlenose dolphin, Tursiops truncatus. This complex occurs as a circumferential cluster of discrete tonsil-like aggregations of lymphoid tissues, together with epithelial ducts ("crypts") and occasional mucus secretory units in the extreme lower portion of the intestinal tract. These structures are concentrated in the segment lined by stratified squamous epithelium and extend for a variable distance cephalad from the anal aperture. The tonsils appear to be most active, judged by the amount of lymphoid tissue present, in young animals. Depletion of lymphocytes and cystic enlargement of the crypts, probably representing functional as well as morphological involution, is a consistent feature of older animals.

Quality assurance in anatomic pathology. An information system approach.

Quality assurance (QA) is the outcome-oriented process by which the performance of a complex production operation is evaluated. It is strongly focused on the use of resources and the end product, and is closely related to marketing. The pathologist's product is information, and the practice of anatomic pathology is evaluated as a system for producing and effectively communicating information. Our integrated program for QA in surgical pathology, autopsy pathology, and cytopathology recognizes that several discrete elements make up the sequence leading to communication of the diagnostic opinion. These are control and processing of the specimen, accuracy of diagnosis, timely and clear communication, efficiency in production of information, coherence with institutional programs in QA, and relation to licensing and accreditation agencies. Each of these elements may be tested separately and sources of error reduced so that the validity and cost of the pathologist's prediction will ultimately be limited only by the state of the art and not by any failure of the information system. Several components of QA, especially resource utilization by pathologists, are potentially productive areas for operations research.

Elastosis in the normal aging breast. A histopathologic study of 140 cases.

The incidence and pattern of elastosis of the breast was studied in tissue specimens taken at autopsy from 140 women with clinically normal breasts, ranging in age from 19 through 101 years. Elastosis, presence of excess elastic fibers, while less common in younger women, may be found in nearly half of all women over age 50 years with no breast disease. Elastosis occurs in three sites: diffusely in the stroma, around vessels, and around ducts. In the first two sites, it bears little relationship to age, while periductal elastic tissue appears to accumulate with age, probably reflecting parity, until about age 50 years. Thereafter, it is found at a more or less constant incidence and degree. While it may be associated with breast cancer, periductal elastosis by itself is not a cause for concern. Marked perivascular elastosis is, however, uncommon at any age, and its presence should suggest a special search for carcinoma, if not already evident.

Validation of the laboratory information system.

OBJECTIVE: To present an organized and practical approach to the validation of laboratory information systems. SOURCES: Personal experience, published papers, technical manuals, and Food and Drug Administration guidelines. DATA: Validation of the laboratory information system is the continuing process of proving the system fit for its intended use, initially and over time. It consists in defining, collecting, maintaining, and independently reviewing evidence that the system will perform consistently according to specification. Validation is tedious, difficult, and costly, but it must be done to assure that the system is fit for use and is working according to specification. In addition to professional and licensing bodies, laboratories making blood products fall under the regulatory requirements of the Food and Drug Administration. The buyer of a system is responsible for verifying that the developer has complied with all regulations and that the software products are validated to an appropriate degree, that the hardware is certified to perform its designated functions, that an appropriate period of acceptance testing has been done and documented, and that the system in use performs to specification and is under control. CONCLUSION: System validation demonstrates to all concerned, inside and outside the laboratory, that the laboratory information system manages information well, with the expected accuracy and reliability, file integrity, auditability, and management control.

Rapid detection of fungi in tissues using calcofluor white and fluorescence microscopy.

Rapid intraoperative examination of tissues for fungi is important for the surgical control of infection. Staining of frozen or paraffin-embedded tissues with calcofluor white (CFW) is a rapid nonspecific method for the identification of fungal infection. When viewed with a fluorescence microscope, fungal elements stained with CFW are sharply delineated from surrounding tissue and easily identified. Calcofluor white also stains tissue elements such as keratin, collagen, and elastin, which provide useful landmarks for the examination. To a much lesser degree, bacteria are also stained with CFW.

Myocardial contraction band necrosis in stranded cetaceans.

The term contraction band necrosis describes focal hypercontraction and lysis of small groups of myocardial cells. Contraction band necrosis of the myocardium was identified in 100% of 52 whales and dolphins (cetaceans) stranded along the western coast of the Gulf of Mexico between April 1991 and November 1996. The myocardial lesions in the cetaceans were identical, both grossly and histologically, to those previously described in man and other animals. Such lesions may contribute to the high mortality rate in stranded cetaceans.

The reliability of fine-needle aspiration biopsy in the diagnosis of deep lesions of the lung and mediastinum: experience with 250 cases using a modified technique.

Two-hundred and fifty discrete lesions of the lung and mediastinum were sampled by a modified fine-needle aspiration biopsy (FNAB) technique. Aspirates were collected directly into 15 ml of Saccomanno's fixative, and all preparative work was carried out in the cytopathology laboratory. Only seven aspirates were "insufficient for diagnosis," giving a productivity rate of 97%. Five insufficient aspirates later proved to be neoplasms. Of the 243 cases with a primary FNAB diagnosis, 21 had insignificant disease, 29 had benign neoplasms or nonneoplastic disease, and 193 had malignant tumors. Most malignancies could be assigned to a specific histologic type by FNAB; those that proved difficult by FNAB were usually difficult on histopathologic examination. There were no false-positive diagnoses of malignancy and only eight false-negative results. Of 12 results interpreted as "suspicious," 10 proved to be malignant on follow-up. This modified method has proven to have a low complication rate and to be both highly productive and reliable in the diagnosis of malignant and nonmalignant disease.

Experience with a modified fine-needle aspiration biopsy technique in 533 breast cases.

Aspiration cytology depends on skillful preparation of smears, which normally requires a trained cytotechnologist. Collection of aspirates into Saccomanno fixative permits preparation of high-quality smears by trained technologists no matter who does the aspiration. Aspiration by a surgeon was used with palpation and mammography to examine 533 patients in an office-based regional breast health program. Lesions sampled ranged from diffuse thickening to frank tumors. Lesions suspicious to any one of the three examinations were biopsed. Cytologically diagnosable material was obtained in 349 instances: 120 were malignant, 22 suspicious, 12 atypical, and 195 benign. Of the 184 yielding insufficient cells, 116 were benign on palpation and mammography, and 68 were suspicious. Biopsy proved 57 of these benign and 11 malignant. There were no cytologic false positives in the study. There was a 2% false-negative rate on productive aspirates. Nonproductive aspiration occurred in 4.8% of malignant cases.