PubMed Health⌕ Search

Biomedical subjects

M R Schwartz

Publications and source records attributed to M R Schwartz.

At least 19 recordsLinked to original sources

Carcinoma with thymus-like differentiation arising in the dermis of the head and neck.

Carcinoma exhibiting thymus-like differentiation (CASTLE) is a rare, distinct tumor of the thyroid gland or soft tissue of the head and neck that may simulate primary squamous cell carcinoma or lymphoepithelioma, and which contains features reminiscent of thymic differentiation including Hassall's corpuscles, occasional perivascular spaces, and the presence of lymphocytes. Ectopic thymic tissue may result from incomplete descent or persistence of the cervical portion of the thymus and may occur anywhere along the course of the embryonic descent from the angle of the mandible to the sternal notch. Herein, we report two cases of dermal extrathyroidal CASTLE. The differential diagnosis of squamoid carcinoma with features of thymic differentiation includes extrathyroidal CASTLE, a primary squamous cell carcinoma with thymic differentiation, lymphoepithelioma-like carcinoma of the skin, and metastatic squamous cell carcinoma of unknown primary. It is essential that the latter two be ruled out before accepting the diagnosis of an extrathyroidal carcinoma with thymus-like differentiation.

Adult↗

Surface markers expressed by multipotent human and mouse neural progenitor cells include tetraspanins and non-protein epitopes.

Surface molecules play important roles in a wide range of cellular functions, yet little has been reported regarding the expression of such markers by neural stem cells. Here, multipotent human neural progenitor cells (hNPCs) were expanded as a monolayer in the presence of fibroblast/epidermal growth factor, harvested, labeled with monoclonal antibodies, and analyzed by flow cytometry. Positive markers included CD9, CD15, CD81, CD95 (Fas), GD(2) ganglioside, and major histocompatibility complex class I and beta2 microglobulin, as well as low levels of the hematopoietic stem cell marker CD34. Of these, mouse NPCs were positive for CD9, CD15, CD81, and GD(2) ganglioside. The markers reported here have been implicated in a wide range of cellular functions including proliferation, migration, differentiation, apoptosis, and immune recognition.

Animals↗

Should the cytologic diagnosis of "atypical squamous cells of undetermined significance" be qualified? An assessment including comparison between conventional and liquid-based technologies.

BACKGROUND: The diagnosis of atypical squamous cells of undetermined significance (ASCUS) remains an enigma for the treating physician, because it encompasses both benign, reactive, as well as preneoplastic and possibly neoplastic conditions. To address this problem, The Bethesda System recommends qualifying the ASCUS diagnosis. This study analyzes the difference in the follow-up results between the various groups of patients with an ASCUS diagnosis as outlined by the Criteria Committee: favor premalignant (ASCUS-P), favor reactive (ASCUS-R), and unqualified (ASCUS-C). The outcome, based on follow-up biopsies and/or cytologies, for both the conventional Papanicolaou smear (CS) and liquid-based (LB) methodologies is compared. METHODS: The CS and LB biopsies and/or cytologies included 590 patients and 137 patients, respectively, who had an initial diagnosis of ASCUS. The final outcome after subsequent biopsy and cytology within a 1-year period for each methodology was tabulated. Furthermore, the addition of qualifiers for each diagnosis was tabulated for both cytology and biopsy follow-up and compared between CS and LB technologies. RESULTS: For CS, 29 patients (8.6%) were found to have squamous intraepithelial lesions (SIL) on subsequent cytologic smears, and 176 patients (63.7%) had SIL on biopsy follow-up. For LB, these numbers were 17 patients (19.1%) and 56 patients (65.1%), respectively. Regardless of the qualification used in the initial CS biopsy or cytology, over 90% of the subsequent smears resulted in a benign diagnosis. Biopsy outcomes after CS diagnoses of ASCUS-P, ASCUS-R, and ASCUS-C showed SIL in 80%, 53%, and 66% of patients, respectively. For LB diagnoses, subsequent smears detected SIL in 33% of patients with a diagnosis of ASCUS-P, 22% of patients with a diagnosis of ASCUS-R, and 12% of patients with a diagnosis of ASCUS-C. Biopsy outcomes after LB diagnoses of ASCUS-P, ASCUS-R, and ASCUS-C showed SIL in 68%, 64%, and 66% of patients, respectively. CONCLUSIONS: There appears to be no statistically valid benefit from a clinical point of view in qualifying an ASCUS interpretation by either CS or LB, except for CS evaluation of patients with a diagnosis of ASCUS-P.

Biopsy↗

Review article: Mycobacterium avium subsp. paratuberculosis as one cause of Crohn's disease.

A number of theories regarding the aetiology of Crohn's disease have been proposed. Diet, infections, other unidentified environmental factors and immune disregulation, all working under the influence of a genetic predisposition, have been viewed with suspicion. Many now believe that Crohn's disease is a syndrome caused by several aetiologies. The two leading theories are the infectious and autoimmune theories. The leading infectious candidate is Mycobacterium avium subspecies paratuberculosis (Mycobacterium paratuberculosis), the causative agent of Johne's disease, an inflammatory bowel disease in a variety of mammals including cattle, sheep, deer, bison, monkeys and chimpanzees. The evidence to support M. paratuberculosis infection as a cause of Crohn's disease is mounting rapidly. Technical advances have allowed the identification and/or isolation of M. paratuberculosis from a significantly higher proportion of Crohn's disease tissues than from controls. These methodologies include: (i) improved culture techniques; (ii) development of M. paratuberculosis-specific polymerase chain reaction assays; (iii) development of a novel in situ hybridization method; (iv) efficacy of macrolide and anti-mycobacterial drug therapies; and (v) discovery of Crohn's disease-specific seroreactivity against two specific M. paratuberculosis recombinant antigens. The causal role for M. paratuberculosis in Crohn's disease and correlation of infection with specific stratification(s) of the disorder need to be investigated. The data implicating Crohn's as an autoimmune disorder may be viewed in a manner that supports the mycobacterial theory. The mycobacterial theory and the autoimmune theory are complementary; the first deals with the aetiology of the disorder, the second deals with its pathogenesis. Combined therapies directed against a mycobacterial aetiology and inflammation may be the optimal treatment of the disease.

Animals↗

Detection of Mycobacterium avium subspecies paratuberculosis in Crohn's diseased tissues by in situ hybridization.

OBJECTIVES: Reports about the association between Crohn's disease (CD) and cell wall-deficient (CWD) forms of Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) are controversial. This may be due to the heterogeneous nature of CD where only about 50% of the patients show granulomatous inflammation. Detection of CWD forms of M. paratuberculosis in tissues from patients with CD would support its association with the disease. To help identify these forms in inflamed tissues, a previously developed and optimized nonradioactive in situ hybridization method was applied on well-defined tissue materials obtained from patients with CD, ulcerative colitis (UC), and controls. METHODS: Specimens from 37 patients with CD (15 with epitheloid cell granulomas and 22 without granulomas), 21 UC, and 22 noninflammatory bowel disease (IBD) patients were analyzed by the in situ hybridization method based on the digoxigenin-labeled M. paratuberculosis IS900 fragment, previously shown to be species specific. Samples were counterstained with hematoxylin and eosin to show the location of the positive signal. Positive controls made of beef cubes injected with CWD and acid-fast M. paratuberculosis and negative controls were included in each experiment to monitor for nonspecific hybridization or staining. RESULTS: Six of 15 (40%) patients with CD and granulomas showed positive signals in myofibroblasts and macrophages. Interestingly, no positive signals were observed within granulomas. Only 4.5% of 22 CD samples from patients with nongranulomatous disease, 9.5% of 21 UC, and remarkably, none of the 22 non-IBD patients were M. paratuberculosis positive. CONCLUSION: The demonstration of DNA from CWD forms of M. paratuberculosis in this limited number of CD tissues further supports and confirms previous reports of its association with the granulomatous type of the disease.

Adult↗

Fas ligand expression in esophageal carcinomas and their lymph node metastases.

BACKGROUND: Although esophageal adenocarcinomas (EADCA) have been shown to have substantially reduced or absent Fas expression, the status of Fas ligand (FasL) in these tumors, especially adenocarcinomas, is largely unknown. METHODS: Using immunohistochemistry, the authors investigated FasL expression in sections of formalin fixed, paraffin embedded tissue from 13 EADCA. They also studied sections of 15 esophageal squamous cell carcinomas (ESCCA) and of lymph node metastases from 7 EADCA and 4 ESCCA. The percentage of FasL positive cells in each tumor was recorded. FasL expression in EADCA was compared with that in ESCCA and with lymph node status. Statistical analysis was performed using the Fisher exact test. RESULTS: No specific staining pattern was seen in adenocarcinomas. In ESCCA, FasL was often located in the cells at the periphery of tumor nests. All (100%) of EADCA showed FasL expression in greater than 25% of the cancer cells, and all were associated with lymph node metastasis. Fifty-three percent of ESCCA showed FasL expression in greater than 25% of the cancer cells and 33% had lymph node metastasis. Expression of FasL in greater than 25% of tumor cells was associated with a significantly higher incidence of lymph node metastasis (P=0.0001). All lymph node metastases from esophageal carcinomas showed FasL immunoreactivity in greater than 50% of the metastatic tumor cells. CONCLUSIONS: FasL expression in greater than 25% of cancer cells correlates with a high incidence of lymph node metastasis in esophageal carcinomas. All cancer metastases in lymph nodes express FasL in >50% of the cells. These findings indicate that FasL plays an important role in the immune evasion and metastasis of esophageal carcinomas.

Adenocarcinoma↗

Comparison of thyroid, auricular, and costal cartilage donor sites for laryngotracheal reconstruction in an animal model.

OBJECTIVE: To evaluate and compare the use of autogenous thyroid cartilage with that of auricular and costal cartilage in laryngotracheoplasty (LTP). DESIGN: A blinded comparison of LTP techniques using anterior thyroid, auricular, or costal cartilage as graft material in a rabbit model. Histological and anatomical analyses were performed on the laryngeal specimens 1, 4, and 6 weeks after surgery. The following factors were analyzed in each specimen: graft viability, cartilage proliferation, perichondrial viability, degree of necrosis, inflammatory response, and degree of epithelialization. SUBJECTS: Fifty-seven New Zealand adult male rabbits, aged 6 months, were divided into 3 study groups (19 animals in each group) initially and equally into the 3 time periods. RESULTS: No episodes of respiratory compromise occurred in any of the animals in the 3 study groups. Gross inspection of the laryngotracheal complex in the thyroid cartilage group revealed no evidence of laryngeal structural compromise. There was no statistical difference between the 3 types of cartilage used for reconstruction for the variables of graft or perichondrial viability, degree of necrosis, or inflammatory response at 1, 4, or 6 weeks. Cartilage proliferation in the thyroid cartilage group was decreased compared with that in the other 2 groups at 1 week. The amount of proliferation increased in this group and was equal to the amount present in the other 2 groups 4 and 6 weeks after surgery. Complete epithelialization of the graft material was present in all 3 groups at 4 and 6 weeks after reconstruction. CONCLUSIONS: The use of autogenous thyroid cartilage for LTP compares favorably with that of other methods of reconstruction that use either auricular or costal cartilage in the rabbit model. This technique is a viable alternative for single-stage LTP and has the added advantage of using a single incision.

Animals↗

Optimized cyclin D1 immunoperoxidase staining in mantle cell lymphoma.

Mantle cell lymphoma (MCL) has a worse prognosis than MALT lymphoma (MALTL). Distinction between MCL and MALTL on purely morphologic grounds can be difficult. Cyclin D1 (PRAD1/bcl1) is overexpressed in MCL as a result of a t(11:14) gene rearrangement, which leads to overexpression of cyclin D1 mRNA and protein. The immunohistochemical detection of cyclin D1 in MCL has been reported by several authors to be highly specific with sensitivity ranging from 70%-100%, but diagnostic laboratories have reported difficulty in finding a reliable method for cyclin D1 immunostaining. The aim of this study was to evaluate and optimize a method for detection of cyclin D1 by paraffin section immunoperoxidase staining. Sections of routinely processed tissue from five MCL and one splenic marginal zone lymphoma (MZL) were immunostained using a mixture of two primary monoclonal antibodies and a standard avidin-streptavidin method. Antigen retrieval was performed using 1) steam heat in citrate buffer, 2) as in "1" followed by sonication for one minute, and 3) as in "2" followed by enzymatic digestion. All the above were repeated, with the additional use of catalyzed signal amplification (CSA). Later, sections of the same cases, plus three MALTL were immunostained as in "2". Steam heat antigen retrieval alone produced the best results. All MCL showed positive nuclear staining while the MZL and all MALTL were negative. Sonication did not enhance staining noticeably, whereas enzymatic digestion produced cytoplasmic staining. CSA increased background staining with no significant gain in nuclear stain intensity. We conclude that cyclin D1 immunostaining of formalin-fixed, paraffin-embedded tissue can be reliably achieved by heat induces antigen retrieval and a cocktail of two monoclonal antibodies.

Antibodies, Monoclonal↗

Qualitative analysis of value judgments in interpreting cervicovaginal smears using the Bethesda system.

CONTEXT: We hypothesize that there are unrecognized value judgments that influence cytopathologists in interpreting borderline cervicovaginal smears and that these judgments contribute to the well-documented variation among cytopathologists regarding such diagnoses. OBJECTIVE: To identify and map these values. DESIGN: Survey consisting of Kodachromes and histories for 5 borderline smears. Respondents were asked to give their diagnoses, recommendations for treatment, and reasoning. RESULTS: We demonstrated a wide variation in interpretation of borderline smears similar to previous studies. We then used inductive qualitative analysis to identify the clinical reasoning and value judgments that influenced the responses. CONCLUSIONS: We mapped those diagnostic value judgments that should be used in evaluation borderline cases. We believe this map can be used to rigorously manage and standardize the use of such judgments.

Adult↗

Overexpression of Fas ligand (FasL) during malignant transformation in the large bowel and in Barrett's metaplasia of the esophagus.

Esophageal and colorectal adenocarcinomas overexpress Fas ligand (FasL), which can protect them from immune surveillance. The aim of this work was to determine whether FasL expression, and therefore FasL-dependent immune evasion, occurs early during malignant transformation in Barrett's metaplasia (BM) of the esophagus, and in the large intestine. Sections of formalin-fixed and paraffin-embedded tissue from esophageal and large bowel biopsies and resection specimens were immunostained for FasL using standard immunoperoxidase technique. The percentage of positive cells was correlated with the degree of dysplasia in BM and with the size and villous architecture of colorectal adenomas. In BM, FasL was detected in 55% of cases negative for dysplasia, and was associated with inflammation in almost all positive cases. By contrast, all cases of BM (100%) with low- or high-grade dysplasia were FasL-positive. In the large intestine, 25% of small adenomas were negative for FasL, and FasL overexpression was significantly more frequent in larger adenomas and in adenomas with tubulovillous or villous morphology. Our results suggest that (1) FasL overexpression is acquired early during malignant transformation of BM and the large bowel and (2) FasL overexpression occurs relatively earlier during malignant progression of BM than the large bowel, probably as a result of the preceding repeated inflammation.

Adenocarcinoma↗

Completely laparoscopic resection of a rare pyloric tumor with laparoscopically sutured gastroduodenostomy.

We report the case of a 31-year-old woman who presented with epigastric pain and weight loss. Esophagogastroduodenoscopy revealed a submucosal mass in the distal antrum and pylorus. Endoscopic biopsy of the mass was nondiagnostic. A CT scan confirmed a 3.0-cm mass in the posterior wall of the distal antrum. She underwent laparoscopic resection of the distal antrum and pylorus with end-to-end gastroduodenostomy. Pathologic examination showed an adenomyoma of the antrum and pylorus. Her postoperative course was uncomplicated, and she continues to do well 38 months postoperatively. Gastric adenomyoma is a rare, benign intramural tumor of the antrum and pylorus. Fewer than 40 cases have been described in the literature. The lesions are generally within 4 cm of the pylorus. Histologically, they are characterized by ductal structures lined by cuboidal to columnar epithelium surrounded by smooth muscle bundles and, occasionally, Brunner's-type glands and heterotopic pancreas. Treatment is by resection, and recurrence has not been reported. Laparoscopic resection of portions of the stomach has been reported. Side-to-side gastrojejunostomies (Billroth II) performed laparoscopically have been reported. This is the first report in the English-language literature of a completely laparoscopically performed sutured gastroduodenostomy. Technical details of the procedure and adenomyomas are discussed.

Adenomyoma↗

Oncocytic mucoepidermoid carcinoma of the salivary glands.

Two parotid mucoepidermoid carcinomas with predominant oncocytic features were initially assessed on frozen section. Because of extensive oncocytic change, it was inferred that the lesions were most likely benign. Permanent sections revealed low-grade mucoepidermoid carcinoma with prominent oncocytic change (in more than 75% of the neoplasms) in both cases. Review of 48 additional consecutive cases of mucoepidermoid carcinoma of the salivary glands revealed prominent oncocytic change (accounting for 60% of the neoplasm) in one high-grade lesion. Phosphotungstic acid-hematoxylin stains revealed strong granular cytoplasmic staining in the oncocytic elements; immunohistochemical stains for antimitochondrial antibodies also showed intense immunoreactivity in these cells. Oncocytic change is not typically a prominent feature of mucoepidermoid carcinoma of the salivary glands, and to our knowledge, only three such cases have been reported previously. Because most salivary gland lesions with oncocytic change are benign, it is important to distinguish mucoepidermoid carcinoma from other entities that may show prominent oncocytic change. We report three additional examples of this rare lesion, two low-grade tumors and one high-grade tumor, and review our experience with oncocytic change in mucoepidermoid carcinoma of the salivary glands.

Adult↗

The role of open rhinoplasty in the management of nasal dermoid cysts.

The nasal dermal sinus cyst is one of many midline nasal masses that often pose diagnostic and treatment dilemmas for the plastic and reconstructive surgeon. The differential diagnosis of the midline nasal mass includes both congenital and acquired processes. A thorough understanding of its cause is crucial to treatment. A comprehensive discussion of the pathogenesis, diagnosis, sequelae, and surgical management, and a representative case analysis, of the nasal dermal sinus cyst is presented to delineate the role of open rhinoplasty in optimizing the care of this congenital nasal deformity.

Adolescent↗

The role of open rhinoplasty in the management of nasal dermoid cysts.

The nasal dermal sinus cyst is one of many midline nasal masses that often pose diagnostic and treatment dilemmas for the plastic and reconstructive surgeon. The differential diagnosis of the midline nasal mass includes both congenital and acquired processes. A thorough understanding of its cause is crucial to treatment. A comprehensive discussion of the pathogenesis, diagnosis, sequelae, and surgical management, and a representative case analysis, of the nasal dermal sinus cyst is presented to delineate the role of open rhinoplasty in optimizing the care of this congenital nasal deformity.

Adolescent↗

Metastatic carcinoma of the prostate mimicking primary carcinoid tumor of the lung and mediastinum.

Although prostatic carcinomas rarely present as intrathoracic metastases, they may occasionally exhibit clinical and radiographic findings suggestive of a primary pulmonary carcinoid, particularly when they have a cribriform pattern. This report describes three patients who presented with lung and mediastinal neoplasms initially diagnosed as primary carcinoid tumors. These tumors were later proven to be metastatic prostate carcinoma by the use of immunohistochemical studies, including stains for chromogranin, carcinoembryogenic antigen and prostate specific antigen. These findings emphasize the importance of considering metastatic prostate adenocarcinoma in the differential diagnosis of carcinoid or neuroendocrine carcinoma with a cribriform pattern.

Adenocarcinoma↗