Daniel F. Cowan

Desmoplastic Small Round Cell Tumor of the Lung

An extra-abdominal desmoplastic small round cell tumor (DSRCT) of the lung with immunohistochemical, ultrastructural, and cytogenetic evidence of multidirectional differentiation is reported. We demonstrate that DSRCTs of the lung and pleura show morphologic, molecular, genetic, and ultrastructural features similar to DSRCTs arising in other sites. The tumor showed coexpression of cytokeratins (AE1/3, epithelial membrane antigen, CAM 5.2) and mesenchymal markers (vimentin, desmin, neuron-specific enolase), as well as WT1. Ultrastructurally, intracytoplasmic whorls of intermediate filaments, similar to previous descriptions of DSRCT in nonthoracic sites, were also demonstrated in this case. EWS-WT1 gene fusion characteristic of DSRCT with the t(11;22)(q13;q12) translocation was demonstrated in this tumor.

High resolution imaging of epithelial injury in the sheep cervicovaginal tract: a promising model for testing safety of candidate microbicides.

Background: Access to readily available large animal models and sensitive noninvasive techniques that can be used for the evaluation of microbicide-induced changes in tissue could significantly facilitate preclinical evaluations of microbicide safety. The sheep cervicovaginal tract, with stratified squamous epithelium similar to humans, holds promise as a large animal model used before nonhuman primates. In addition, optical coherence tomography (OCT) could enable high resolution visualization of tissue morphology and noninvasive assessment of microbicide-induced epithelial injury. Methods: We evaluated the dose response of sheep cervicovaginal tract to benzalkonium chloride (BZK). Twenty sheep received treatment with phosphate-buffered saline or BZK solution (2%, 0.2%, or 0.02%). Pre- and posttreatment colposcopy and OCT images were collected and graded based on World Health Organization criteria and a previously reported scoring system, respectively. Biopsies were collected and the degree of epithelial injury and its thickness was assessed based on histology and OCT. Results: The sheep cervicovagina exhibited anatomic and microscopic features similar to the human. Extensive loss of the epithelium was noted on colposcopy and OCT after application of 2% BZK. Colposcopy detected findings in half of sheep and OCT in all sheep treated with 0.2% BZK. OCT detected differences in the 0.02% BZK-treated group compared with controls, whereas colposcopy failed to detect any changes. Conclusions: The sheep cervicovagina is similar to humans, and exhibits dose dependent epithelial changes after BZK treatment. These findings suggest that the sheep model and OCT may become valuable tools for the safety evaluation of candidate microbicides, and warrant continued development.

Morphology of the lymphoid organs of the bottlenose dolphin, Tursiops truncatus

The anatomy of the lymphoid organs was studied during the course of detailed dissections of 50 beach‐stranded bottlenose dolphins, Tursiops truncatus. Constant lymph nodes occur in 4 groups, based on their location and structure. These groups are somatic, including nodes of the cervical region and pelvic recess; lung‐associated, included marginal, diaphragmatic and hilar nodes; visceral, including the mesenteric, pancreatic, pericolic and porta hepatis nodes; and aortic arch nodes. Lymphatic drainage of the lung is primarily to the marginal and diaphragmatic nodes. The mesenteric node mass is well‐endowed with capsular and trabecular smooth muscle, and a network of muscle fascicles within the organ implies an important contractile function in the circulation of lymph. In addition to constant nodes, occasionally nodes are found in relation to the thoracic aorta, the kidney, and under the scapula. Gut‐associated structures include dorsal and ventral oropharyngeal tonsils, mucosal aggregates in the straight segment of the intestine (colon) and anal tonsils; this gut‐associated lymphoid tissue tends to involute with age, being greatly reduced by puberty. Formed lymphoid organs include the thymus and the spleen, the latter being relatively small in relation to body size. None of these structures is unique among cetaceans, but the anal tonsils are particularly well developed in T. truncatus. The lymphoid aggregates in the colon resemble the arrangement in the vermiform appendix, which is lacking in most cetaceans, and may have functions analogous to that organ.

Basaloid Squamous Cell Carcinoma of the Esophagus With or Without Adenoid Cystic Features

CONTEXT Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare malignant tumor that morphologically could bear some resemblance to adenoid cystic carcinoma (ACC) originating from salivary glands. OBJECTIVE The purpose of this study is to describe the histologic, immunohistochemical, and ultrastructural findings of BSCCs of the esophagus, with an emphasis on comparing tumors with or without adenoid cystic features. DESIGN We reviewed 239 cases of primary esophageal carcinoma and detected 12 cases (5%) of BSCC. The light and electron microscopic findings and immunocytochemical localization of various antigens, including cytokeratins (AE1, AE3), carcinoembryonic antigen, epithelial membrane antigen, S100, smooth muscle actin, and p53, were examined in these BSCC cases. RESULTS Histologically, all BSCCs were composed of solid lobules or nests of basaloid cells with well-demarcated outlines surrounded by a fibrous stroma. Seven of 12 tumors showed areas of ACC-like features, that is, cribriform-like pseudoglandular lumina formation and hyaline material surrounding the tumor nests, whereas the remaining 5 tumors were apparently pure basaloid carcinomas. These 2 groups of tumors were histologically and immunohistochemically identical in many aspects, namely, high-grade nuclei of the tumor cells with frequent mitoses, abundant comedo-type necrosis, focal areas of concomitant squamous differentiation, consistent immunoreactivity for cytokeratins, and poor or absent staining for S100 and smooth muscle actin. Ultrastructurally, the basaloid tumor cells exhibited relatively undifferentiated cellular characteristics and undeveloped cell organelles. CONCLUSION Basaloid squamous cell carcinomas of the esophagus frequently have an intimate association with ACC-like patterns, but their histologic, immunocytochemical, and ultrastructural features correspond more to poorly differentiated squamous cell carcinoma than to salivary gland ACC. This distinction is important because genuine ACC is much less aggressive than BSCC.

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.

Thyrolipoma and thyrolipomatosis: 5 case reports and historical review of the literature.

Because thyrolipoma (adenolipoma of thyroid) and thyrolipomatosis (diffuse lipomatosis of thyroid) are distinctively rare conditions with only few cases reported in the literature, we are reporting 5 additional cases. All the 5 patients were adult females, with ages from 38 to 79 years, who presented with thyroid masses. Four of the patients had normal thyroid function tests and one had mild hypothyroidism. All patients received partial or total thyroidectomy. The thyroid specimens showed either circumscribed yellow-tan masses (cases 1, 2, and 3) or diffuse yellow-brown discoloration (cases 4 and 5). Histologic examination revealed abundant mature fat infiltrating the affected thyroid tissue in 3 distinct patterns: (1) fat infiltration limited to follicular adenomas (thyrolipoma); (2) fat diffusely infiltrating throughout the thyroid gland (thyrolipomatosis); or (3) fat infiltration involving both follicular adenoma and their surrounding thyroid tissue. Because of the rarity of thyroid fat-containing lesions, confusion in differential diagnosis may occasionally occur. It is important to be aware during frozen section that these lesions may present as extrathyroidal nodules, which can be radioactive on intraoperative scan for parathyroid glands. In addition, a papillary thyroid carcinoma was also identified in one case of thyrolipomatosis. All patients recovered well after surgery and there has been no recurrence of the lesions after 1 to 24 years of clinical follow-up. In summary, we are reporting 5 rare cases of thyrolipoma and thyrolipomatosis with distinct histologic patterns. Previously reported cases of thyrolipomatosis were reviewed and analyzed with the current cases.

Histopathological Evaluation of Laser Thermocoagulation in the Human Prostate: Optimization of Laser Irradiation for Benign Prostatic Hyperplasia

We have previously shown in a canine prostate model that a noncontact low power neodymium:YAG laser regimen of 15 watts for 180 seconds yields a larger volume of coagulation necrosis than the currently recommended high power regimen of 50 watts for 60 seconds. These 2 regimens have not yet been compared in humans. The objective of this study was to evaluate histopathologically the thermocoagulation effect of these 2 laser regimens in the human prostate and the effect of the spatial distribution of the laser lesions on the extent of coagulation necrosis. The study was conducted in 10 patients undergoing radical prostatectomy or cystoprostatectomy. The laser treatment was given transurethrally 1 hour before removal of the specimen. There were no fractures of the prostate. The coagulation necrosis did not reach the peripheral zone and it was minimal in areas rich in fibromuscular tissue, such as the bladder neck. At times, nodular benign prostatic hyperplasia was unaffected. A 4-quadrant treatment in the same plane often yielded small nonconfluent lesions. Confluent lesions in the same plane yielded approximately 30% greater depth of coagulation necrosis, which was achieved when 3 or 4 lesions were created on each side of the prostate (per single transverse plane). Likewise, coagulation necrosis observed with 15 watts for 180 seconds was approximately 40% greater than that noted with the 50 watts for 60 seconds regimen. Our findings suggest that noncontact laser prostatectomy is a safe procedure that can be improved by modifying the laser regimen and the spatial distribution of lesions.

Adaptations to diving hypoxia in the heart, kidneys and splanchnic organs of harbor seals (Phoca vitulina)

SUMMARY Pinnipeds (seals and sea lions) have an elevated mitochondrial volume density [VV(mt)] and elevated citrate synthase (CS) andβ -hydroxyacyl-CoA dehydrogenase (HOAD) activities in their swimming muscles to maintain an aerobic, fat-based metabolism during diving. The goal of this study was to determine whether the heart, kidneys and splanchnic organs have an elevated VV(mt) and CS and HOAD activities as parallel adaptations for sustaining aerobic metabolism and normal function during hypoxia in harbor seals (Phoca vitulina). Samples of heart, liver, kidney, stomach and small intestine were taken from 10 freshly killed harbor seals and fixed in glutaraldehyde for transmission electron microscopy or frozen in liquid nitrogen for enzymatic analysis. Samples from dogs and rats were used for comparison. Within the harbor seal, the liver and stomach had the highest VV(mt). The liver also had the highest CS activity. The kidneys and heart had the highest HOAD activities, and the liver and heart had the highest lactate dehydrogenase (LDH) activities. Mitochondrial volume densities scaled to tissue-specific resting metabolic rate [VV(mt)/RMR] in the heart, liver, kidneys, stomach and small intestine of harbor seals were elevated (range 1.2-6.6×) when compared with those in the dog and/or rat. In addition, HOAD activity scaled to tissue-specific RMR in the heart and liver of harbor seals was elevated compared with that in the dog and rat (3.2× and 6.2× in the heart and 8.5× and 5.5× in the liver, respectively). These data suggest that organs such as the liver, kidneys and stomach possess a heightened ability for aerobic, fat-based metabolism during hypoxia associated with routine diving. However, a heightened LDH activity in the heart and liver indicates an adaptation for the anaerobic production of ATP on dives that exceed the animals aerobic dive limit. Hence, the heart, liver, kidneys and gastrointestinal organs of harbor seals exhibit adaptations that promote an aerobic, fat-based metabolism under hypoxic conditions but can provide ATP anaerobically if required.

Isolation of fungal rDNA from bottlenose dolphin skin infected with Loboa loboi

Fungal-specific primers targeted for highly conserved genomic nucleic acid sequences were used in a polymerase chain reaction (PCR) to amplify DNA from lobomycosis lesions in a bottlenose dolphin. Sequence alignments of this DNA possessed high homology to fungal ribosomal DNA sequences found in the genus Cladosporium. When used for in situ hybridization, the riboprobe transcribed from a cloned PCR-generated fragment bound to Loboa loboi cells. These results support the hypothesis that L. loboi in dolphin tissue is a fungus.

Organ Weights and Growth Profiles in Bottlenose Dolphins (Tursiops truncatus) from the Northwestern Gulf of Mexico

Systematic necropsies were performed on 63 bottlenose dolphins (Tursiops truncatus), and data on organ mass, standard body length (SBL), body mass (BM), gender, sexual maturity, and age were measured and/or estimated. Animals were extremely fresh and recovered from along the Texas and Louisiana coastline in the northwestern Gulf of Mexico. Organ reference tables were established for this species to facilitate comparisons with other bottlenose dolphins and to provide a baseline for other cetacean species. Organs examined included lungs, adrenal glands, kidneys, testes, ovaries, heart, liver, pancreas, brain, pituitary, thyroid, thymus, and spleen. Individuals were separated into three size classes: 225 cm, based on SBL to further facilitate comparisons. Growth rates of length and mass were described using Gompertz nonlinear models as a function of gender. No sexual dimorphism was identified in BM or organ weights, and SBL was only significantly larger for older mature males. SBL and BM were strongly correlated with age when all animals were included in analyses, although this is not an accurate predictor of age, especially in older individuals. Organ weights were significantly correlated with both SBL (except thymus and spleen) and BM (except left ovary, spleen, and thymus). Age was significantly correlated with all organ weights (except thymus, thyroid, and ovaries). There were no significant differences in the weight of any paired organs (adrenal glands, kidneys, lungs, ovaries, testes), and all were significantly correlated with BM. These data on organ weights of bottlenose dolphins, when interpreted with SBL, BM, and age, are significant tools for pathologists and veterinarians interpreting animal health status.