The pathology fellowship application crisis: The current state and suggestions for remediation.

Problems within the Pathology fellowship application process in the US have been recognized and reported for years. Recently, members of the Graduate Medical Education Committee (GMEC) of the Association of Pathology Chairs (APC) and collaborators collected survey data from the residents themselves and the fellowship programs, as represented by both the fellowship program directors (members of the Fellowship Directors Ad Hoc Committee, FDAHC) and the program administrators (members of the Graduate Medical Education Administrators Section, GMEAS). These data are presented and discussed, and potential steps to resolve some of the problems around fellowship applications in pathology are presented.

Analysis of Alternative Food Sources for Rearing Entomological Evidence.

Forensic entomology is a well-established tool for evaluating the death, or abuse, of a person. Insect evidence provides valuable information as related to time of colonization and movement of remains from one location to another. Blow flies (Diptera: Calliphoridae) are commonly found on human remains throughout most stages of decomposition, and when entomological evidence is collected these taxa tend to be the most numerous.

Tumor Cell Detection by Mass Spectrometry Using Signal Ion Emission Reactive Release Amplification.

A method is presented for the detection of circulating tumor cells (CTC) using mass spectrometry (MS), through reporter-ion amplification. Particles functionalized with short-chain peptides are bound to cells through antibody-antigen interactions. Selective release and MS detection of peptides is shown to detect as few as 690 cells isolated from a 10 mL blood sample.

Discovery of N-(4-Fluoro-3-methoxybenzyl)-6-(2-(((2S,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)-2H-tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A Highly Selective and Orally Bioavailable Matrix Metalloproteinase-13 Inhibitor for the Potential Treatment of Osteoarthritis.

Matrix metalloproteinase-13 (MMP-13) is a zinc-dependent protease responsible for the cleavage of type II collagen, the major structural protein of articular cartilage. Degradation of this cartilage matrix leads to the development of osteoarthritis. We previously have described highly potent and selective carboxylic acid containing MMP-13 inhibitors; however, nephrotoxicity in preclinical toxicology species precluded development.

Cancer prevention trial of a synergistic mixture of green tea concentrate plus Capsicum (CAPSOL-T) in a random population of subjects ages 40-84.

Background: Experts agree that one of the more promising strategies in cancer management is early detection coupled with early intervention. In this study, we evaluated an early cancer detection strategy of cancer presence based on serum levels of the cancer-specific transcript variants of ENOX2 in serum coupled with an ENOX2-targeted nutraceutical preparation of green tea concentrate plus Capsicum (Capsol-T®) as a strategy of Curative Prevention® involving early detection coupled with early intervention in early stage cancer when in its most susceptible and manageable stages.

Experimental Design: One hundred ten (110) subjects were tested for cancer presence using the ONCOblot® Tissue of Origin 2-D gel/western blot protocol for detection of serum presence of transcript variants of the ENOX2 protein.

Synthesis and biological evaluation of substituted benzoxazoles as inhibitors of mPGES-1: use of a conformation-based hypothesis to facilitate compound design.

Microsomal prostaglandin E(2) synthase-1 (mPGES-1) is a novel therapeutic target for the treatment of inflammation and pain. In the preceding letter, we detailed the discovery of clinical candidate PF-04693627, a potent mPGES-1 inhibitor possessing a novel benzoxazole structure. While PF-04693627 was undergoing further preclinical profiling, we sought to identify a back-up mPGES-1 inhibitor that differentiated itself from PF-04693627.

Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis.

Potent, highly selective and orally-bioavailable MMP-13 inhibitors have been identified based upon a (pyridin-4-yl)-2H-tetrazole scaffold. Co-crystal structure analysis revealed that the inhibitors bind at the S(1)(') active site pocket and are not ligands for the catalytic zinc atom. Compound 29b demonstrated reduction of cartilage degradation biomarker (TIINE) levels associated with cartilage protection in a preclinical rat osteoarthritis model.

A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in interleukin-1 beta-stimulated synovial fibroblasts.

NF-kappa B-induced gene expression contributes significantly to the pathogenesis of inflammatory diseases such as arthritis. I kappa B kinase (IKK) is the converging point for the activation of NF-kappa B by a broad spectrum of inflammatory agonists and is thus a novel target for therapeutic intervention. We describe a small molecule, selective inhibitor of IKK-2, SC-514, which does not inhibit other IKK isoforms or other serine-threonine and tyrosine kinases.

Cytologic findings of myxoid neurothekeoma: case report based on fine-needle aspiration cytology, immunohistochemistry, and correlating histopathology.

Myxoid neurothekeomas (nerve sheath myxomas) are rare benign cutaneous neoplasms that may morphologically mimic other myxoid neoplasms of skin and soft tissue. The cytologic and histopathologic features of this lesion may resemble various myxoid sarcomas, chordoma, myxoid neurofibroma, dermal cutaneous mucinosis, and cutaneous myxoma as well as other myxoid or chondroid neoplasms. In this study, a myxoid neurothekeoma was analyzed using multiple techniques.

Mortality rates and number of deaths from cardiovascular diseases in Italy from 1982 to 1993. A comparison with total and tumour data.

In this study the recent Italian trends in cardiovascular deaths and mortality are described and compared with the trends regarding total and tumour deaths and mortality. The data, collected from the National Institute of Statistics, are presented as total (T), tumour (TU), cardiovascular (CV), cerebrovascular (CVD), ischemic heart disease (IHD) standardized mortality (sm), non-standardized mortality (nsm) and absolute number of deaths (d), according to sex, age, and geographical area. Data on sm were available only for the age group <75 years old.

Fine-needle aspiration biopsy in the evaluation of lymphadenopathy associated with cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome).

We studied the role of fine-needle aspiration (FNA) in the evaluation of lymphadenopathy associated with cutaneous T-cell lymphoma (CTCL) in 11 patients with lymphadenopathy and compared findings with corresponding histologic material. Molecular genetic analysis for T-cell clonality by polymerase chain reaction (PCR) was performed on all aspirates. Immunophenotyping was successful in 4 of 7 cases in which flow cytometry was attempted from the aspirated material.

The role of p53, p21WAF1/C1PI, and bcl-2 in radioresistant colorectal carcinoma.

Genetic alterations in the p53 tumor suppressor gene are common in human colorectal cancers, occurring in approximately 70% of tumors. In vitro studies have shown that wild-type p53 is involved in controlling cell cycle checkpoint functions and apoptosis involved in the cytotoxic response induced by ionizing radiation and several anticancer chemotherapeutic agents. Wild-type p53 protein can transcriptionally activate the WAF gene, which encodes a cyclin-dependent kinase inhibitory protein, p21WAF1/C1PI protein, and transcriptionally repress the bcl-2 gene, which encodes an inhibitor of apoptosis.

The case for cytologic follow-up after LEEP.

Objective: To examine our loop electrocautery excisional procedure (LEEP) biopsy experience to assess the incidence of abnormal follow-up and relate this to margin status.

Study Design: Records of 162 LEEP procedures performed between January 1992 and April 1994 were reviewed to evaluate margin readability and status. All follow-up cytologic or histologic specimens were examined.

Cervical endometriosis: a potential pitfall in the evaluation of glandular cells in cervical smears.

The use of the cytobrush and other endocervical sampling instruments has resulted in an increasing rate of detection and attention to glandular abnormalities of the cervix. Lesions that have been identified as look-alikes to endocervical gland dysplasia or adenocarcinoma in situ include squamous carcinoma in situ, atypical squamous metaplasia involving glands, and tubal metaplasia. In this report, we describe our recent experience with another condition that can mimic glandular abnormalities--cervical endometriosis.

The detection of endocervical gland involvement by high grade squamous intraepithelial lesions in smears prepared from endocervical brush specimens.

The cytologic features of squamous cell carcinoma in situ with endocervical gland involvement have been described in cervical smears. We evaluated the presence of two types of cellular fragments in 43 cervical smears of high grade squamous intraepithelial lesions (HGSIL) to assess their ability to predict glandular involvement by HGSIL in subsequent cone biopsies. An endocervical brush was used to obtain all endocervical specimens.

Expression of estrogen and progesterone receptors in cytologic specimens using various fixatives.

Estrogen and progesterone receptor reactivity may be useful in identifying possible primary sites of metastatic disease or directing therapy in tumors of the female genital tract, including breast, ovary, and endometrium. Various methods have been described for the immunocytochemical evaluation of estrogen receptor (ER) and progesterone receptor (PR) status of cytologic specimens but our results have been variable. We evaluated the effectiveness of various fixatives [cytospin collection fluid, Shandon, Pittsburgh, PA (SH); ethanol (ETH); and formalin (FOR)] for fixation of smears (SM) and cell block (CB) material.

Loop electrocautery excisional procedure: therapeutic effectiveness as an ablation and a conization equivalent.

This study was designed to compare the effectiveness of loop excision procedures as ablation and conization equivalents, and their use in recurrent cervical high-grade dysplasia patients. We retrospectively reviewed patients undergoing loop procedures between January 1992 and April 1994. Conization equivalents were defined as procedures performed for unsatisfactory colposcopy, positive endocervical curettage, discordant cytology and histology, and cytology suggestive of invasion.

Endoluminal ultrasonographic and histologic evaluation of periurethral collagen injection.

To determine the acute and chronic ultrasonographic and histologic characteristics of injected glutaraldehyde cross-linked collagen in an animal model in order to enhance the therapeutic efficacy of the delivery of collagen for the treatment of urinary incontinence, three different depths of endoluminal ultrasound-guided injection (submucosal, intramuscular, periadventitial) of collagen into the urethral and bladder walls in two Yucatan mini pigs were investigated. The ultrasonographic characteristics of the injected material were examined 1, 4, 8, and 12 weeks later. A separate set of collagen injections, into the dermis and intramuscular layer of the lateral thigh of the animals, was undertaken with small-parts ultrasound guidance and follow-up.

Malignant melanoma of the vulva: a review.

Vulvar melanoma is an unusual tumor with a poor prognosis. Most surgeons have abandoned radical vulvectomy as the treatment of choice. The role of elective node dissection is controversial.

Bcl-2 oncoprotein is widespread in lymphoid tissue and lymphomas but its differential expression in benign versus malignant follicles and monocytoid B-cell proliferations is of diagnostic value.

The distribution of Bcl-2 oncoprotein was studied immunohistochemically in formaldehyde-fixed and paraffin-embedded reactive and neoplastic lymphoid tissue. The potential of Bcl-2 for the differential diagnosis of follicular lesions was emphasized, and the results on follicular lesions were correlated with those of polymerase chain reaction (PCR) assay of the immunoglobulin heavy chain gene rearrangement. In hyperplastic lymphoid tissue, Bcl-2 reactivity was widespread, including germinal center surroundings, scattered cells within the germinal centers, and the T-cell areas in general.

Bilateral breast carcinoma: mammographic and histologic correlation.

Purpose: To determine the mammographic, histologic, and clinical features of bilateral breast cancer.

Materials And Methods: Pre-biopsy mammograms of 67 patients with bilateral carcinoma were reviewed. Lesions were synchronous in 35 patients and metachronous in 32.

Solitary fibrous tumor: histological and immunohistochemical spectrum of benign and malignant variants presenting at different sites.

Twenty-nine tumors (from 26 patients, including two with recurrent disease) diagnosed as solitary fibrous tumor (SFT) of the pleura (n = 23), mediastinum (n = 4), abdominal cavity (n = 1), and parotid gland (n = 1) were studied immunohistochemically. Three histologically malignant tumors showed areas of high cellularity and mitotic activity (more than 4 mitoses/10 high-power fields) with features resembling malignant fibrous histiocytoma, malignant hemangiopericytoma, or fibrosarcoma, together with areas typical of benign solitary fibrous tumor. Formaldehyde-fixed, paraffin-embedded tissues and avidin-biotin-complex immunostaining were used.

Histopathological heterogeneity in fulminant hepatic failure.

The clinicopathological features of 38 patients admitted consecutively for fulminant hepatic failure were studied. Histopathological material was reviewed in all patients. Both percutaneous and whole livers (either explanted or autopsy specimens) were available in 16 patients: whole livers only in 12 patients and biopsy specimens only in 10 patients.

Predictors of human papilloma virus in patients with keratinization.

Given the prevalence of human papilloma virus (HPV) infection, an attempt was made to determine whether certain factors such as keratinization and/or squamous atypia are associated with its development. Review of our gynecologic cytology files from 1989 yielded 1,615 specimens showing parakeratosis and/or hyperkeratosis, without cytologic evidence of HPV. Concomitant diagnoses included no atypia [keratinization only (KO)], inflammatory squamous atypia (ISA), and squamous atypia (SA).