Stephen E. Vernon

Low-Grade Fibromyxoid Sarcoma: A Brief Review

Low-grade fibromyxoid sarcomas are uncommon deep soft tissue neoplasms first described by Evans in 1987. They exhibit a deceptively benign appearance, with a whorled or linear arrangement of spindle-shaped cells showing few to absent mitoses. A characteristic, but not specific, feature is the presence of areas of myxoid stroma. Recurrences are common, and late metastases have been recorded. A closely related but morphologically distinct tumor, the so-called hyalinizing spindle cell tumor with giant rosettes, has also been described; both neoplasms share the same cytogenetic abnormality, a balanced translocation resulting in a FUS/CREB3L2 fusion gene. Because of similar clinical behavior and the common cytogenetic abnormality, some authors prefer to consider both lesions as a single entity within the spectrum of low-grade sarcomas.

Pre-Treatment and Post-Treatment Evaluation of Prostatic Adenocarcinoma for Prostatic Specific Acid Phosphatase and Prostatic Specific Antigen by Immunohistochemistry

Prostatic specific acid phosphatase and prostatic specific antigen have been used as specific markers of prostatic adenocarcinoma in immunohistochemical studies, particularly when seeking the primary site of a poorly differentiated metastasis. We herein evaluate the effect of therapy on the persistence of these markers in surgically obtained tissues. Prostatic biopsies from 30 patients with adenocarcinoma of the prostate gland before and after treatment with orchiectomy alone, diethylstilbestrol, external beam radiation or combined radiation and diethylstilbestrol were studied for prostatic specific acid phosphatase and prostatic specific antigen using the indirect immunoperoxidase technique. The interval between biopsies ranged from 3 to 72 months, with an average of 28 months. All pre-treatment biopsies stained positively for prostatic specific acid phosphatase and prostatic specific antigen. Staining for prostatic specific antigen and prostatic specific acid phosphatase was seen easily in 29 of 30 post-treatment biopsies, while in 1 case infiltrating anaplastic cells surrounded by stroma showed staining for these antigens in an extremely small percentage of cells, which were overlooked easily unless examined carefully. In view of this small number of positively staining cells this case was designated as equivocal. While some cases demonstrated less intense staining in post-treatment biopsies compared to pre-treatment, this finding was by no means constant. With these primary antisera a higher percentage of cytologically malignant cells stained positively for prostatic specific acid phosphatase than for prostatic specific antigen in adjacent tissue sections in some cases. Prostatic specific acid phosphatase and prostatic specific antigen appear to be sensitive and persistent markers of prostatic adenocarcinoma despite morphologic changes accompanying various therapies.

Angiotropism of Human Melanoma: Studies Involving In Transit and Other Cutaneous Metastases and the Chicken Chorioallantoic Membrane: Implications for Extravascular Melanoma Invasion and Metastasis

Melanoma cell migration along the outside of vessels has been termed “extravascular migratory metastasis” (EVMM), as distinct from intravascular dissemination. Previous studies in both human and experimental melanoma models have shown angiotropism of melanoma cells, suggesting EVMM. Our objectives are to study the mechanism of dissemination of human melanoma cells in the chick chorioallantoic membrane (CAM) and to compare the histopathology in the CAM with that of patients with in transit and other cutaneous melanoma metastases.Human and murine melanoma cells were inoculated onto the CAM and observed over a 10-day period for tumor dissemination. Both human melanoma specimens from 26 patients and melanoma cells growing on the CAM showed the presence of tumor cell angiotropism at the invasive front of the tumor and at some distance from the tumor mass. In addition, a clear progression of melanoma cells spreading on the CAM was observed along the abluminal surface of vessels, where they occupied a perivascular location. By day 10 after injection, small micrometastases had developed along vessels, in a pattern similar to that in transit and other cutaneous melanoma metastases. In addition, the results suggested that the number of micrometastases directly correlated with increasing tumor volume. Taken together, these data suggest that the CAM is a relevant model for studying tumor cell dissemination, and that EVMM may be a mechanism by which some melanoma cells spread to nearby and even distant sites.

Angiotropism of human prostate cancer cells: implications for extravascular migratory metastasis

To report several samples of invasive human prostate cancer showing angiotropism, and to use human prostate cancer cells stably expressing green fluorescence protein (GFP) in in vitro and in vivo models to assess the dissemination pathway of prostate cancer cells.

Overexpression of malignancy‐associated laminins and laminin receptors by angiotropic human melanoma cells in a chick chorioallantoic membrane model

Background: As distinct from intravascular/lymphatic dissemination, extravascular migratory metastasis (EVMM) has been described as a potential additional mechanism of melanoma spread in which tumor cells migrate along the external surfaces of vessels. Angiotropic melanoma cells are linked to the endothelium by a matrix containing laminin. In addition, it has been shown that C16 laminin‐derived peptide increases extravascular migration of human green fluorescent protein (GFP) melanoma cells along vessels in a chicken chorioallantoic membrane model (CAM). In this study, we have tested the hypothesis that expression levels of some genes related to lamimin and metastasis are differentially expressed in vascularized angiotropic melanoma areas vs. avascular melanoma areas from the same tumor.

Continuous Throughput Rapid Tissue Processing Revolutionizes Histopathology Workflow

and laboratory automation have ushered in a new age in histopathology. In conventional histopathology laboratories, current practices are essentially unchanged for more than 50 years, and in fact probably for much longer. Routine use of formalin fixation, overnight dehydration and paraffin infiltration, and manual embedding and sectioning have served us well in producing relatively uniform, high-quality tissue sections for histopathologic examination. As we move into the 21st century, however, these methods are seriously deficient in prompt diagnoses and answers to questions clinicians and patients are now asking, particularly with respect to the identification of gene activation and detection of gene products such as messenger RNA (mRNA) and proteins. Since 1997, we have been developing a tissue processing system which eliminated the use of formaldehyde and xylene, and used microwave energy to facilitate the diffusion of reagents and denaturation of proteins, as has been previously reported.1 This system has been extensively studied and automated instruments have been developed which allow for continuous throughput, shortening the processing time to about 70 minutes. The method also reduced the volume of other chemicals used in processing. The resulting histologic preparations are at least comparable to traditional hematoxylin and eosin stained slides for older methods (Image 1), and immunohistochemical staining is also comparable (Image 2) and in some cases enhanced (lower concentrations of primary antibodies needed). Other microwave-based tissue processes have recently been described with similar good results.2 Once the method was established and proven to be practical, issues of implementation had to be addressed. Histopathology is a field steeped in tradition (we’ve always done it that way), and overcoming resistance to change represented a major undertaking. I have divided these changes into several categories for consideration: Where we work, 2) How we work, and 3) When we work. The following are observations related to each of these categories.

Gallbladder cystadenoma and common bile duct obstruction.

Cystadenomas are usually found in the extra-hepatic bile ducts in conjunction with multilocular cysts in the liver. Cystadenoma of the gallbladder itself is a rare finding, cited only once in the literature as the cause of extrinsic obstruction of the common bile duct (5). In this report, we describe the endoscopic retrograde cholangiopancreaticographic (ERCP) detection of intrinsic obstruction of the cystic duct and common bile duct by such a tumor in a 47-yr-old woman.

Basal Cell Carcinoma of the Scrotum: A Case Report and Literature Review

Basal cell carcinoma of the scrotum is a rarely occurring lesion that must be differentiated from the more common squamous cell carcinoma, as well as chronic dermatitis or chronic fungal infection. We report a case of basal cell carcinoma of the scrotum and review the literature. This case serves as a reminder that these lesions do occur on the scrotal skin and that, unlike squamous cell carcinomas, they are curable with simple wide excision.

Cutaneous zygomycosis associated with urate panniculitis.

Cutaneous zygomycosis is being increasingly recognized as a serious and life-threatening infection in debilitated and immunosuppressed patients, including transplant patients. The organisms are morphologically distinct but difficult to grow in cultures from clinical samples. We report a case of cutaneous zygomycosis in a neonatal multi-visceral organ transplant patient, with subcutaneous panniculitis accompanied by extensive local acicular uric acid crystal deposition. Although the patients serum uric acid was subsequently found to be in the normal range, transient hyperuricemia could not be excluded. Because we use a microwave-based processing system avoiding aqueous solutions, the crystals were maintained in the tissue sections and were shown by various methods to consist of monosodium urate. Early diagnosis combined with extensive debridement and prompt antifungal therapy resulted in a successful outcome. We have coined the term “urate panniculitis” to describe this phenomenon.

Middle Ear Packing Comparison of Materials in an Animal Model of Mucosal Trauma

Objective. To compare absorbable gelatin sponge (AGS) with an injectable esterified hyaluronic acid (EHA) as middle ear packing material after mucosal trauma. Study Design. Randomized, blinded, and controlled study. Setting. Tertiary university-based hospital. Subjects and Methods. Twenty-three guinea pigs underwent middle ear surgery with mucosal trauma performed on both ears and one ear packed with either EHA or AGS. Contralateral ears were used as nonpacked paired controls. Auditory brainstem response (ABR) thresholds were measured preoperatively and repeated at 1, 2, and 6 weeks postoperatively. Macroscopic and microscopic analysis measured inflammatory reaction in each group. Results. ABR threshold changes from baseline in the EHA and both control groups were minor. Threshold levels were higher in the AGS group compared with the AGS control group. This trend was seen in each frequency tested at each time interval. Macroscopic analysis showed tympanic membrane perforation was rare, effusions were common in the AGS group, mucosal edema was most frequent in the AGS group, and unabsorbed packing was usually detected in the AGS group with little EHA detectable at 6 weeks. Microscopic analysis showed normal mucosal healing in all groups. Two AGS ears demonstrated excessive middle ear packing with exuberant osteoneogenesis. Conclusions. Middle ear function and mucosal healing after surgery occurred similarly between the EHA control group and the EHA group. In contrast, the AGS group demonstrated worse hearing and a greater level of osteoneogenesis compared with the AGS control group. These results support EHA as an alternative middle ear packing material in otologic surgery.