bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocyte Transdifferentiation
Authors: d'Amati Giulia , di Gioia Cira R. T. , Giordano Carla , Gallo Pietro
Published: January 2021

Adipose substitution of ventricular myocardium is characteristic of arrhythmogenic right ventricular cardiomyopathy, but is also found in other heart conditions. It is thought to be a consequence of myocyte loss due to myocarditis or other noxious stimuli. We describe a unique case of cardiomyopathy with a morphologic pattern suggestive of transdifferentiation from myocytes to mature adipocytes. Gross, histologic, and ultrastructural examination were performed on the heart of a female transplant patient with a clinical diagnosis of familial dilated cardiomyopathy. Gross examination showed fibroadipose substitution of the left ventricle and adipose replacement of the right. Histology, immunohistochemistry, and ultrastructure were highly suggestive of transdifferentiation from cardiac muscle to adipose tissue. Myocyte transdifferentiation could represent an alternative pathogenetic pathway to the myocyte-loss and adipose-replacement mechanism in arrhythmogenic right ventricular cardiomyopathy, or it could be the basis of a new type of familial cardiomyopathy.
Acute Myelomonocytic Leukemia With Histologic Features Resembling Sarcomatoid Carcinoma in Bone Marrow
Authors: Hamoudi Walid H. , Jeffrey L. , Townsend Gault , Glassman Armand B. , Bueso-Ramos Carlos E.
Published: January 2021

We report a case of primary acute myelomonocytic leukemia involving the bone marrow that resembled sarcomatoid carcinoma. The neoplastic cells in bone marrow biopsy specimens formed cohesive-appearing clusters and cords separated by an immature fibroblastic proliferation and myxoid stroma. Blasts in the bone marrow aspirate smears formed clusters and sheets, and a subset of blasts exhibited erythrophagocytosis. Dysgranulopoiesis was also present. Lineage was confirmed by immunohistochemical analysis of formalin-fixed, paraffin-embedded tissue. The tumor cells showed strong reactivity for lysozyme, myeloperoxidase, CD45, and CD68 and were negative for keratin, S100, CD20, and CD3. The serum lysozyme concentration (110 μg/mL) was 13 times greater than the normal value (8 μg/mL). Cytogenetic studies performed on bone marrow aspirate material revealed a complex karyotype, including trisomy 8 and abnormalities of chromosome 11q. We report this case of acute myelomonocytic leukemia because the neoplastic cells appeared cohesive and spindled, resembling sarcomatoid carcinoma, and therefore caused diagnostic difficulty. Other monocytic neoplasms with similar resemblance to carcinoma or sarcoma have been reported in the literature, suggesting that the tendency to appear cohesive may be an inherent characteristic of neoplastic cells with monocytic differentiation.
A Unique Method for Mutation Analysis of Tumor Suppressor Genes in Colorectal Carcinomas Using a Crypt Isolation Technique
Authors: Sugai Tamotsu , Habano Wataru , Nakamura Shin-ichi , Uesugi Noriyuki , Sasou Shunichi , Itoh Chuichi
Published: January 2021

Background.—Contamination of nontumor tissue makes genetic analysis difficult. For this reason, it is important to obtain pure tumor tissue to ensure accurate genetic analysis.

Objective.—To accurately assess the incidence of mutation of tumor suppressor genes (p53: exon 5–8; APC: mutated cluster region; NF-2 gene: all exons) in 45 colorectal carcinomas.

Methods.—We developed an application of the polymerase chain reaction–single-strand conformation polymorphism and DNA sequence by coupling them with crypt isolation.

Results.—Mutations of p53 and APC genes were found in 24 and 22 of 45 colorectal carcinomas, respectively. No mutation of the NF-2 gene was observed in this cancer. Single-strand conformation polymorphism using a crypt isolation technique showed a clear migrating band and no false-positive data.

Conclusions.—The crypt isolation technique is a useful method for accurately analyzing genetic alterations. Furthermore, our proposed method confirmed the morphological findings obtained before the genetic analysis.
Analysis of False-Negative Diagnoses on Endoscopic Brush Cytology of Biliary and Pancreatic Duct Strictures
Authors: Logrono Roberto , Kurtycz Daniel F. , Molina Claudia P. , Trivedi Vipul A. , Wong Jick Y. , Block Kevin P.
Published: January 2021

Context.—Endoscopic brush cytology is a valuable technique for the diagnosis of pancreatobiliary malignancy. Despite its widespread use, the sensitivity of this method has been reported as approximately 50%. The specificity is usually higher than 95%. Few reports have systematically analyzed the reasons for this relatively low sensitivity.

Objectives.—To determine the rate and reasons for false-negative diagnoses in endoscopic brushing cytology of biliary and pancreatic ducts based on the results of sensitivity, specificity, accuracy, and positive and negative predictive values.

Design.—Retrospective analysis of laboratory data and slide review of false-negative cases.

Setting.—Two tertiary care state university hospitals.

Patients.—A total of 183 pancreatobiliary brushing specimens obtained from patients undergoing endoscopic retrograde cholangiopancreatography for biliary or pancreatic duct disease for a 4- to 5-year period.

Intervention.—Endoscopic retrograde cholangiopancreatography brushings.

Main Outcome Measures.—Determination of sensitivity, specificity, accuracy, and positive and negative predictive values. Analysis of false-negative results.

Results.—The sensitivity, specificity, accuracy, and positive and negative predictive values, overall, were 48%, 98%, 79%, 92%, and 76%, respectively. Sampling error was a major cause of false-negative diagnoses (67%), followed by interpretive (17%) and technical errors (17%).

Conclusions.—Improvements in sensitivity and diagnostic accuracy for cancer of the pancreatobiliary tract can be achieved by optimizing slide preparatory techniques. Also, enhancement of the cytologist's diagnostic skills enables the identification of the morphologic features of premalignant lesions. Repeat brushings are indicated for suspicious or negative results not consistent with the clinical or radiologic findings.
Esophageal Collision Tumor (Large Cell Neuroendocrine Carcinoma and Papillary Carcinoma) Arising in a Barrett Esophagus
Authors: Wilson Christopher I. , Summerall Janna , Willis Irvin , Lubin Jack , Inchausti Beria Cabello
Published: January 2021

We report herein a unique case of an esophageal collision tumor composed of a papillary adenocarcinoma and a large cell neuroendocrine carcinoma arising in a Barrett esophagus. Hematoxylin-eosin and silver staining patterns, immunohistochemistry, and electron microscopy of the large cell neuroendocrine component are discussed.
The Cytomorphology of Pleuropulmonary Blastoma
Authors: Nicol Kathleen K. , Geisinger Kim R.
Published: January 2021

Pleuropulmonary blastoma is a rare, primitive primary neoplasm of the thorax in young children. The tumor, which is often but not always associated with cystic lung lesions, may arise in pulmonary parenchyma, the mediastinum, and pleura. Histologically, it is characterized by a biphasic neoplastic population of undifferentiated-appearing small round cells and larger spindle-shaped cells. A proportion of these cancers may also manifest more specific mesenchymal differentiation. In contrast to the pulmonary blastoma of adults, a malignant epithelial component does not occur. We present herein the third known case of a fine needle aspiration biopsy of a pleuropulmonary blastoma in a 5-year-old girl. The smears were moderately cellular and included an admixture of the characteristic small ovoid blastemal elements and scattered spindled mesenchymal tumor cells.
Morning Rounds Inpatient Test Availability
Authors: Novis David A. , Dale Jane C.
Published: January 2021

Objectives.—To determine the success with which laboratories were able to report morning test results on time, the laboratory practice characteristics associated with improved success, and the degree of satisfaction among clinicians with the timeliness of laboratory service.

Design.—Hospital laboratories participating in the College of American Pathologist Q-Probes laboratory quality improvement program prospectively calculated the percentages of morning-run complete blood cell count (CBC) and electrolyte results that were reported on or before predetermined reporting deadlines, completed questionnaires concerning their departments' practice characteristics as they related to performing morning blood work, and distributed to physician utilizers of morning laboratory services questionnaires evaluating physician satisfaction with laboratory services.

Setting and Participants.—A total of 367 public and private institutions located in the United States (355), Canada (5), Australia (2), and 1 each in the United Kingdom, Spain, Brazil, Korea, and Guam.

Main Outcome Measure.—The percentages of morning-run CBC and electrolyte results reported on or before predetermined reporting deadlines.

Results.—Participants submitted data on 40 256 CBC and 39 604 electrolyte specimens. In aggregate, a total of 88.9% of these tests (90.2% of CBCs and 87.6% of electrolytes) were reported on or before the reporting deadlines that the participating laboratories set for themselves. Half of the participants reported 94.6% of their CBC results and 95.5% of their electrolyte results on or before their self-imposed reporting deadlines. No specific demographic features or departmental practice characteristics were associated with higher or lower rates of institutional reporting compliance. Most physician utilizers of early-morning laboratory test results believed that the laboratory is sensitive to and meets the needs of clinicians for timely reporting of early-morning test results.

Conclusions.—Most laboratories are capable of reporting 95% of their routine morning laboratory tests on time, and most physicians are satisfied with their laboratories' morning testing service.
Immunoexpression of Inhibin α Subunit, Inhibin/Activin βA Subunit and CD99 in Ovarian Tumors
Authors: Choi Yoon-La , Kim Hy-Sook , Ahn Geunghwan
Published: January 2021

Objective.—Anti–inhibin α and inhibin/activin βA subunit and anti-CD99 monoclonal antibodies (mAbs) have recently been demonstrated to be able to label ovarian granulosa cells; thus, they may be of value in the diagnosis of granulosa cell tumors. The present study aimed to determine what combination of these mAbs may be useful for the differential diagnosis of sex cord–stromal tumors of ovary.

Design.—Immunohistochemical analyses with anti–inhibin α and inhibin/activin βA subunit antibody and anti-CD99 mAb were performed on 42 ovarian tumors, including sex cord–stromal tumors (29), ovarian epithelial cancers (10), and Krukenberg tumors (3).

Results.—All sex cord–stromal tumors were positive for inhibin α subunit, and 17 cases (58.6%) of sex cord–stromal tumors were immunoreactive for inhibin/activin βA subunit. Epithelial tumors and Krukenberg tumors were all negative for inhibin/activin βA subunit except mucinous carcinoma, which showed strong cytoplasmic immunoreactivity. All sex cord–stromal tumors except one granulosa cell tumor showed membranous staining for CD99. A case of serous carcinoma and a case of mucinous carcinoma were positive for CD99, and the remaining epithelial tumors and Krukenberg tumor were all negative for CD99.

Conclusions.—The results of immunohistochemical analysis, together with literature review, suggest that inhibin α subunit may be a useful diagnostic marker for sex cord–stromal tumor of the ovary. In addition, anti-CD99 antibody may be useful for the differential diagnosis between ovarian tumors. Inhibin/activin βA subunit has a limited usefulness in the differential diagnosis of ovarian tumor because of its wider immunoreactivity for both sex cord–stromal tumors and mucinous carcinomas. The differential diagnosis of sex cord–stromal tumors of the ovary would be better made with a combined use of both anti–inhibin α subunit and anti-CD99 mAbs.
Cytologic Atypia in a 53-Year-Old Man With Finasteride-Induced Gynecomastia
Authors: Zimmerman Robert L. , Fogt Franz , Cronin Dennis , Lynch Randall
Published: January 2021

Finasteride has been associated with the development of gynecomastia. Although cytoplasmic vacuolization has been noted in prostatic epithelium in men taking this drug, we found no documentation of the cytologic changes in finasteride-associated gynecomastia. We present the case of a 53-year-old man who developed unilateral gynecomastia following finasteride therapy for alopecia. A fine-needle aspiration biopsy of the mass was diagnosed as adenocarcinoma on the basis of nuclear atypia and particularly because of cytoplasmic vacuolization. Subsequent excisional biopsy revealed benign gynecomastia with no evidence of malignant change. The ductal epithelium did exhibit cytoplasmic vacuolization similar to that described in the prostate following finasteride therapy. We believe this is the first reported case documenting the cytologic changes seen in gynecomastia secondary to finasteride therapy. Cytoplasmic vacuolization in this setting should not be considered evidence of malignancy in men with gynecomastia. As with gynecomastia in general, extreme caution should be used before rendering a cytologic diagnosis of malignancy.
Statistical Issues in Tumor Marker Studies
Authors: Pajak Thomas F. , Clark Gary M. , Sargent Daniel J. , McShane Lisa M. , Hammond M. Elizabeth H.
Published: January 2021

Context.—Inferences from tumor marker studies are complicated by a variety of statistical concerns, which can make proper interpretation of results difficult. This article focuses on important issues that should be addressed when designing, conducting, and analyzing tumor marker studies.

Objective.—To highlight the importance of considering statistical significance, risk ratios, statistical power, reproducibility, multiple testing, confirmatory studies, and missing data in the design of marker studies used for prognosis.

Results.—Suggestions are provided for more effectively conducting marker studies. These include more careful attention to adequacy of the number of subjects for a marker study and improved documentation and standardization of assay methods. The importance of complete reporting of study results and description of the statistical analysis methods used is also emphasized.

Conclusion.—Cooperation among clinicians, laboratory scientists, and statisticians will be required to conduct statistically sound tumor marker studies and to facilitate prioritizing markers for new and confirmatory studies in an environment of limited patient and specimen resources.
Urinary Cytologic Findings in Patients With Benign and Malignant Adenomatous Polyps of the Prostatic Urethra
Authors: Schnadig Vicki J. , Adesokan Adekunle , Neal Durwood , Gatalica Zoran
Published: January 2021

Context.—Urethral adenomatous polyps with prostatic epithelium (also known as benign prostatic epithelial polyps [BPEPs]) are a documented cause of hematuria, dysuria, and hematospermia, conditions that may prompt cytologic evaluation of urine.

Design.—The urine cytologic test findings in 5 cases of biopsy-proven BPEPs and in 1 case of prostatic ductal adenocarcinoma (PDA) that presented as a urethral polyp were retrospectively evaluated. Immunocytochemical stain for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and high-molecular-weight cytokeratin (34βE12) were used in evaluation of the lesions.

Results.—In 4 of 5 cases of BPEPs, clusters of bland columnar cells with uniform, oval nuclei were seen. Positive immunostaining for PSA and PAP confirmed the prostatic origin of the clusters in 2 cases. One urine sample contained abundant goblet cells and extracellular mucin, consistent with intestinal metaplasia coexisting in the bladder biopsy specimen. The urine sample in the fifth case of BPEPs contained no columnar cells. The last case had multiple urine cytologic evaluations that demonstrated PSA-positive, malignant-appearing clusters of columnar cells. A biopsy specimen of the polyps was described as a high-grade prostatic intraepithelial neoplasm in adenomatous polyp. However, in this patient, PDA was diagnosed on transurethral resection of the prostate specimen 4 years after the initial urine cytologic test.

Conclusion.—Benign prostatic epithelial polyps should be considered in the differential diagnosis of clusters of columnar cells in urine cytologic testing. Cells with malignant nuclear features should instigate a careful search for a (prostatic) neoplasm, which may present as urethral polyps (eg, PDA). Stains for PSA or PAP are useful adjuncts in differential diagnosis of this condition.
Improvement in Physician's Office Laboratory Practices, 1989–1994
Authors: St. John Tina M. , Lipman Harvey B. , Krolak John M. , Hearn Thomas L.
Published: January 2021

Background.—In 1986 and 1989, the Centers for Disease Control and Prevention sponsored institutes on Critical Issues in Health Laboratory Practice. It was noted during the institutes that physician's office laboratories were a rapidly emerging site for clinical laboratory testing, yet no comprehensive data were available regarding the practice of clinical laboratory medicine in physician's office laboratories. As a mechanism to begin addressing this void, the Centers for Disease Control and Prevention added questions on clinical laboratory practice to the National Ambulatory Medical Care Survey, a national probability sample of ambulatory care provided by office-based physicians. Data were collected for survey years 1989, 1991, 1993, and 1994.

Methods.—Each survey was conducted among a nationally representative, random sample of office-based physicians who provide ambulatory patient care. Sample physicians were enlisted using both mail and telephone contacts. Clinical laboratory data were obtained via telephone by trained field representatives. Weighted univariate and multivariate analyses were performed on responses from each of the 4 survey years. Analyses were repeated after combining survey responses from years 1989 and 1991 and 1993 and 1994 as representative of physician's office laboratory practices before and after implementation of the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88) final rule in 1992.

Results.—Quality laboratory practice indicators showed significant increases during the study interval, with implementation of the CLIA ’88 final rule in 1992 playing a pivotal role. Relative to 1992, enrollment in proficiency testing programs increased from 32.4% to 52.7% (P < .001), use of daily quality control samples increased from 79.2% to 89.0% (P < .001), and use of daily quality control with written instructions for action following a questionable quality control result (quality control with action step documentation) increased from 62.6% to 77.2% (P < .001). The presence of a medical technologist or technician in the office laboratory was also significantly and independently associated with each of the quality indicators. Although the percentage of physician's offices performing on-site testing decreased from 56% to 45% during the survey interval, overall testing volume appeared unchanged.

Conclusions.—The quality of clinical laboratory practice in physician's office laboratories improved during the study interval (1989–1994) as measured by the quality indicators used in the study. The association of this improvement with implementation of the CLIA ‘88 final rule and the presence of a trained laboratory professional in the testing site indicate the importance of minimum practice standards and professional expertise in ensuring use of quality laboratory practices. Overall test volume appeared to be stable despite a decreased proportion of physician's offices at which on-site testing was performed.
Decreased CD10-Positive Mature Granulocytes in Bone Marrow From Patients With Myelodysplastic Syndrome
Authors: Chang Chung-Che , Cleveland Ronald P.
Published: January 2021

Objective.—We retrospectively examined the maturation of the granulocytic cell lineage in bone marrow specimens from patients with myelodysplastic syndrome (MDS) by flow cytometry using both light scatter and surface marker characteristics, including CD10 and myeloid lineage–associated antigens.

Patients.—The 7 MDS cases we studied included 2 patients with refractory anemia (RA), 3 with RA with ringed sideroblasts, 1 with RA with excess of blasts, and 1 unclassified case. Another 7 patients matched for age and sex who received bone marrow aspirates for lymphoma staging (all negative for lymphoma involvement or any other hematologic abnormalities) were selected as the control group.

Results.—The percentage of CD10+ mature granulocytes was significantly lower in patients with MDS than in control patients. Additionally, all patients with MDS had less than 50% CD10+ cells in the granulocytic lineage. In contrast, only 1 of the 7 control patients had less than 50% CD10+ cells (P < .01).

Conclusions.—These results suggest that flow cytometry might be a useful adjunct in the assessment of patients with suspected MDS. Further studies to correlate CD10+ mature granulocytes from MDS cases with other benign hematologic disorders are indicated to confirm our evaluation.
A Case Report of Ascariasis of the Common Bile Duct in a Patient Who Had Undergone Cholecystectomy
Authors: Amog Glenda , Lichtenstein Jeffrey , Sieber Steven , El-Fanek Hani
Published: January 2021

This is a case report of ascariasis of the common bile duct in a 65-year-old man from Colombia who had undergone prior cholecystectomy. The patient presented with postprandial epigastric pain and a 20-lb weight loss. The laboratory findings were remarkable for peripheral blood eosinophilia. The ultrasound finding was suggestive of periampullary or pancreatic neoplasm. He underwent endoscopic retrograde cholangiopancreatography with endoscopic extraction of a motile, live worm identified as Ascaris lumbricoides. Roundworm infestation should always be suspected in immigrants from endemic areas who present with hepatobiliary symptoms.
The Surgical Pathology and Cytopathology of US Persian Gulf War Military Veterans
Authors: Specht Charles S. , Lewin-Smith Michael R. , Kalasinsky Victor F. , Peterson Michael R. , Mullick Florabel G.
Published: January 2021

Background.—Tens of thousands of Persian Gulf War veterans (GWVs) have presented with medical symptoms since Operation Desert Shield and Operation Desert Storm. The Kuwait Registry at the Armed Forces Institute of Pathology was established to act as a repository for surgical pathology, cytopathology, and autopsy material from GWVs.

Objective.—To identify conditions known to be endemic to the theater of operations in our cohort of GWVs.

Methods.—The Kuwait Registry database was searched by computer for listed conditions endemic to the Persian Gulf region included in the registry through December 31, 1997.

Results.—Of the 2582 patients in this cohort, 1 patient with hepatitis B and 15 patients with hepatitis C were identified. Other known endemic conditions of the Persian Gulf region were not found.

Conclusions—Viral hepatitis (B and C), which is prevalent in the US population, was the only listed endemic condition identified in surgical pathology or cytopathology specimens in our cohort of GWVs.
A Micropapillary Variant of Transitional Cell Carcinoma Arising in the Ureter
Authors: Vang Russell , Abrams Jacki
Published: January 2021

A 79-year-old woman was evaluated for a ureteral stricture related to laser ablation of a tumor 6 months earlier at another institution. A ureteroscopic examination revealed an exophytic papillary tumor that was resected and examined histologically. The tumor was characterized by delicate papillae with thin stromal cores and numerous secondary micropapillae lined by small cuboidal to low columnar cells with uniform low-to-intermediate–grade nuclei, reminiscent of a serous borderline tumor of müllerian origin. The cell linings were 1 to 4 layers thick; mitotic figures were easily identified. The underlying stroma appeared edematous and contained scattered chronic inflammatory cells. No invasion was identified. After ascertaining that the patient had no known gynecologic neoplasm, the differential diagnoses considered included papillary nephrogenic adenoma, clear cell carcinoma, and the recently described entity of micropapillary transitional cell carcinoma. Because of the striking resemblance to serous carcinoma and the presence of significant mitotic activity, this case was felt to represent a case of micropapillary transitional cell carcinoma (World Health Organization grade 1 to 2) occurring in the ureter. To our knowledge, this tumor had some unique features (no areas of grade 3 nuclei or invasion) that have not been reported in tumors occurring in the urinary bladder. The transitional cell nature of the tumor cells was supported by the immunohistochemical staining pattern. The anatomic distribution of micropapillary transitional cell carcinoma is now expanded to include the ureter, and this tumor should be considered in the differential diagnosis for papillary lesions occurring in the ureter.
CD8 Expression on B Cells in Chronic Lymphocytic Leukemia
Authors: Islam Anwarul , Vladutiu Adrian O. , Donahue Theresa , Akhter Selina , Sands Amy M. , Ambrus Julian L.
Published: January 2021

The expression of CD8, a restricted T-cell antigen, on B cells in B chronic lymphocytic leukemia is rare, and its significance, if any, remains unknown. We report herein a patient with B chronic lymphocytic leukemia in whom CD8 was strongly expressed on all B cells, both in the bone marrow and peripheral blood. The patient required no therapy for 6 years after being diagnosed as having B chronic lymphocytic leukemia. Then, when the disease progressed, he was treated with conventional doses of fludarabine phosphate (25 mg/m2 daily for 5 days), but unlike other patients with B chronic lymphocytic leukemia he tolerated this therapy poorly. He received a total of only 4 series of fludarabine therapy, and following each course of treatment, he developed considerable myelosuppression. After the fourth course of therapy, his bone marrow failed to show any evidence of regeneration, and he died as a result of intercurrent respiratory tract infection 1 month after his last dose of fludarabine was given.
Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma With Associated Fungal Ball in a Patient With Human Immunodeficiency Virus Infection
Authors: Mhawech Paulette , Krishnan Bhuvenswari , Shahab Imran
Published: January 2021

We describe a case of primary mucosa-associated lymphoid tissue lymphoma of the lung in a 44-year-old man with human immunodeficiency virus. Low-grade pulmonary lymphomas in human immunodeficiency virus–positive patients are rare and are described most commonly in pediatric patients. The gross, histologic, and molecular features of this unusual case are described.
Natural Killer–Cell Lymphoma Involving the Gynecologic Tract
Authors: Mhawech Paulette , Medeiros L. Jeffrey , Bueso-Ramos Carlos , Coffey Donna M. , Gei Alfredo F. , Shahab Imran
Published: January 2021

Non-Hodgkin lymphomas (NHL) can involve the gynecologic tract, most often as a manifestation of systemic involvement, and most cases reported have been of B-cell lineage. We describe 2 women with natural killer (NK)-cell lymphoma involving the gynecologic tract that initially presented with vaginal bleeding. In case 1, the patient had a stage IE nasal-type NK-cell lymphoma involving the cervix. The tumor was composed of medium-sized, irregular lymphoid cells with angioinvasion and necrosis. In case 2, the patient had a stage IV blastoid NK-cell lymphoma/leukemia infiltrating all organs in a hysterectomy and bilateral salpingo-oophorectomy specimen. Subsequent biopsy specimens revealed that the bone marrow and lymph nodes were also involved. The neoplasm was composed of small to medium lymphoid cells with fine nuclear chromatin. Case 1 was assessed immunohistochemically and the neoplastic cells were positive for CD3, CD56, and TIA-1. Case 2 was analyzed using both immunohistochemical and flow cytometry methods. The neoplastic cells were positive for cytoplasmic CD3, CD4, CD7, CD43, CD45, and CD56 and were negative for surface CD3. Both cases were negative for Epstein-Barr virus (EBV) ribonucleic acid (RNA) and molecular studies showed no evidence of T-cell receptor γ chain gene rearrangements. The immunophenotype and absence of T-cell receptor gene rearrangements support NK-cell origin. We report these cases to illustrate that NK-cell lymphomas can involve, and rarely arise in, the gynecologic tract.
Epstein-Barr Virus–Associated High-Grade B-Cell Lymphoma of Mucosal-Associated Lymphoid Tissue in a 9-Year-Old Boy
Authors: Tao Jianguo , Kahn Leonard
Published: January 2021

We report an unusual case of Epstein-Barr virus (EBV)-associated mucosal-associated lymphoid tissue (MALT) lymphoma involving the lungs, kidneys, and axillary lymph nodes in a child with congenital hypoadrenalism and panhypopituitarism. The patient presented with an aggressive clinical course and histologic evolution. Initial biopsies (1994) of the lung and kidney revealed histologic features of low-grade B-cell MALT lymphoma with lymphoepithelial lesions within the renal tubules and bronchial epithelium. Subsequent biopsies (1996, 1997, and 1999) revealed progressively greater cytologic atypia, polymorphism, and necrosis; an increased mitotic rate; and a preponderance of large cells, indicative of progression from a low-grade to a high-grade MALT lymphoma. Immunophenotyping of the lung and lymph node lesions revealed identical surface marker profiles: cells were CD19+, CD20+, immunoglobulin (Ig) G+, κ+, λ−, CD5−, CD10−, CD23−, and IgM−, and also negative for T-cell markers. Genotypic analysis demonstrated the presence of immunoglobulin heavy chain rearrangement and monoclonality of EBV in the lung lesion by Southern blot hybridization and polymerase chain reaction (PCR). The clinicopathologic features suggest that these lesions might represent an immunosupression-related continuum of low-grade to high-grade MALT lymphomas. Infection with EBV may have contributed to this tumor's aggressive clinical and histologic evolution.
Angiomyofibroblastoma of the Male Inguinal Region
Authors: Ito Makoto , Yamaoka Hideyuki , Sano Kenji , Hotchi Masao
Published: January 2021

We present a case of benign angiomyxoid tumor arising in the inguinal region of a 27-year-old man. The tumor was a gelatinous mass completely encapsulated by a thin fibrous capsule with no hemorrhage or necrosis. Histologically, a proliferation of spindle cells as well as occasional pleomorphic cells was observed within the myxofibrous stroma, intermingled with abundant capillary-sized blood vessels. Immunohistochemical staining of the tumor demonstrated spindle, oval, and pleomorphic cells equally positive for vimentin, desmin, and CD34, but not for α-smooth muscle actin. Based on these histologic and immunophenotypic features, we conclude that this angiomyxoid tumor of the male inguinal region is indistinguishable from the female angiomyofibroblastoma of the pelvic and perineal regions.
Follicular Dendritic Cell Sarcoma Presenting as a Submucosal Tumor of the Stomach
Authors: Han Jae-Ho , Kim Se-Hoon , Noh Sung-Hun , Lee Yong-Chan , Kim Ho-Guen , Yang Woo-Ick
Published: January 2021

Follicular dendritic cell (FDC) sarcomas, especially those of extranodal origin, are extremely rare, and this entity could easily be missed without a high index of suspicion. We report a case of FDC sarcoma presenting as a submucosal tumor of the stomach in a 45-year-old man. The mass was a spindle and epithelioid mesenchymal tumor with many individually scattered and perivascular aggregates of lymphocytes. Immunohistochemical and ultrastructural studies confirmed the diagnosis. Although more than 50 cases of this tumor have been documented in the English literature, to our knowledge the presentation of FDC sarcoma as a submucosal tumor of the stomach has never been recorded. This case highlights the occurrence of FDC sarcoma as a submucosal tumor of the gastrointestinal tract. We believe that FDC sarcoma should be included in the differential diagnosis of spindle or epithelioid cell tumors of the gastrointestinal hollow viscus to prevent this still underrecognized tumor from being overlooked.
Cytogenetic Profile of a Thymoma
Authors: Mirza Imran , Kazimi Syed Nadeem , Ligi Richard , Burns Jacqueline , Braza Frank
Published: January 2021

Cytogenetic analysis of mixed lymphocyte and epithelial thymoma in a nonmyasthenic female patient revealed deletion of part of the short arm of chromosome 6. To our knowledge, this cytogenetic abnormality in a benign thymoma has not been previously described in the literature, which is reviewed.
Parotid Gland Malignant Melanomas
Authors: Prayson Richard A. , Sebek Bruce A.
Published: January 2021

Background.—Malignant melanomas are relatively unusual tumors in the parotid gland. The majority of previously reported cases appear to represent metastatic lesions, often from cutaneous head and neck primaries.

Methods.—Retrospective clinicopathologic review of 12 cases of malignant melanoma involving the parotid gland encountered between 1980 and October 1999 at a tertiary referral center.

Results.—Patients consisted of 9 men and 3 women ranging in age from 30 to 84 years (median, 66 years). Eleven of 12 patients presented with a neck mass or nodule. In 9 of 12 patients, a cutaneous or conjunctival primary was noted in the head region. In 2 patients, a cutaneous melanoma and the parotid gland melanoma were diagnosed at the same time. In 1 patient, melanoma was initially diagnosed in the parotid gland, and a definite primary was not uncovered. All patients underwent excision of the parotid melanoma, which was accompanied by a lymph node biopsy or dissection in 10 out of 11 patients. Four patients received adjuvant radiotherapy, and 3 patients received adjuvant chemotherapy. Four of 11 patients had ipsilateral cervical lymph node metastasis at the time of parotid tumor resection, and 5 patients had involvement of intraparotid lymph nodes by metastatic melanoma. Tumors ranged in size from 0.3 to 2.5 cm in greatest dimension. Multiple parotid nodules were noted in 4 patients. All tumors were characterized by a diffuse proliferation of cells with abundant eosinophilic cytoplasm and prominent nucleoli. Four tumors demonstrated focal spindle cell regions. Intravascular and/or lymphatic involvement by tumor within the parotid gland was noted in 3 lesions. At last known follow-up, 6 patients had died with tumor at a median follow-up period of 11 months after parotid gland surgery. Four patients were alive with evidence of tumor at follow-up intervals of 4, 17, 21, and 113 months after parotid gland surgery. Two patients were alive with no evidence of residual tumor at 20 and 148 months of follow-up.

Conclusions.—The majority of melanomas involving the parotid gland appeared to be associated with lymph node metastasis in and around the gland from a cutaneous primary in the head region. Prognosis is generally poor, although rare patients may survive a long period of time following surgery.
Primary Localized Extranodal Hodgkin Disease of the Transverse Colon
Authors: Vadmal Manjunath S. , LaValle Gregory P. , DeYoung Barry R. , Frankel Wendy L. , Marsh William L.
Published: January 2021

Extranodal Hodgkin disease presenting as a primary localized neoplasm is uncommon, with rare case reports describing primary sites other than lymph nodes. The gastrointestinal tract is the most frequent site of involvement by extranodal Hodgkin disease, typically involving the stomach or small bowel. To date, we have been able to find only one fully documented case of Hodgkin disease of the sigmoid colon confirmed by immunohistochemical studies. We report a case of extranodal Hodgkin disease involving the transverse colon, presenting as inflammatory bowel disease and documented by light microscopic, immunohistochemical, cytogenetic, and molecular studies.
Sarcomatoid Renal Cell Carcinoma of Papillary Origin
Authors: Cohen Ronald J. , McNeal John E. , Susman Marleen , Sellner Loryn N. , Iacopetta Barry J. , Weinstein Sydney L. , Dawkins Hugh J. S.
Published: January 2021

Sarcomatoid renal cell carcinoma (SRCC) is an aggressive tumor variant thought to arise predominantly from dedifferentiation of clear cell carcinoma. A few reports of SRCC associated with non–clear cell tumors led to the presumption that SRCC may arise from any renal cell carcinoma, although direct evidence of this is lacking. Cytogenetic studies on 3 previously documented SRCCs associated with papillary renal cancers showed either 3p deletions or absence of trisomy 7, 17 in the sarcomatoid tumors, suggesting origin from a coexistent clear cell tumor. The present case represents the first conclusive evidence of direct progression of non–clear cell carcinoma to SRCC with both tumor components containing multiple copies of chromosomes 7 and 17. Many genetic anomalies, including p53 mutations, frequently recognized in SRCC were not recognized in this case, highlighting the importance of cytogenetic evaluation of all SRCC. The patient is well and without evidence of tumor progression 1 year after surgery, and the sinister outlook of SRCC in association with clear cell carcinoma may not apply in SRCC of non–clear cell origin.
Perspectives in Pharmacogenetics
Authors: Kalow Werner
Published: January 2021

The historical perspective of pharmacogenetics is presented to a large extent from a personal view, since I happened to get into this field of science at the time of its beginning, and since pharmacogenetics has remained the backbone of my scientific career. Pharmacogenetics initially emphasized observations of interpersonal variability, but the attention on interethnic differences soon followed. Technical advances led to the identification of many responsible gene alterations in both individuals and in populations. Included is a relatively extensive discussion in which the effects and the different consequences of monogenic (mendelian) and multigenic (multifactorial) variation are compared.
Cyclin D1 Expression in Dysplastic Nevi
Authors: Ewanowich Carol , Brynes Russell K. , Medeiros L. Jeffrey , McCourty Althea , Lai Raymond
Published: January 2021

Objective.—We previously surveyed cyclin D1 expression in common acquired nevi, Spitz nevi, and malignant melanomas and reported that benign nevi maintain a zonal pattern of cyclin D1 expression, in contrast with malignant melanomas. Our aim was to extend those observations by examining cyclin D1 expression in dysplastic nevi.

Methods.—Cyclin D1 overexpression in 23 dysplastic nevi was detected by an immunohistochemical technique. The extent of atypia of the nevi was graded as mild, moderate, or severe, using previously established criteria.

Results.—Cyclin D1 overexpression in dysplastic nevi maintained a zonal pattern, similar to Spitz nevi. Cyclin D1 overexpression was greatest in the region of the epidermal-dermal junction and was significantly less prominent in the papillary and reticular dermis, suggesting that cyclin D1 expression is under cell control and correlates with maturation of nevus cells. Cyclin D1 overexpression also correlated with cytologic atypia, as dysplastic nevi with moderate or severe cytologic atypia contained a greater percentage of cyclin D1–positive cells than did nevi with mild atypia. Six dysplastic nevi with many cyclin D1–positive cells were assessed by fluorescence in situ hybridization studies using cyclin D1–specific and chromosome 11 centromeric probes. In all cases, there was no evidence of 11q13 translocation, amplification, or trisomy of chromosome 11.

Conclusions.—Cyclin D1 may be involved in the pathogenesis of dysplastic nevi. Cyclin D1 overexpression does not appear to be explained by cyclin D1 locus amplification or translocation in most cases, and it may be a result of other cell abnormalities that up-regulate the protein level of cyclin D1.
The Relation Between Newborn Hemoglobin F Fractions and Risk Factors for Sudden Infant Death Syndrome
Authors: Cochran-Black Diana L. , Cowan Linda D. , Neas Barbara R.
Published: January 2021

Objectives.—The aims of this study were to determine and compare fetal hemoglobin (HbF) fractions at birth in newborns exposed and not exposed to selected factors that have been reported to increase the risk of sudden infant death syndrome (SIDS). Previous studies have implicated HbF in the etiology of SIDS by finding higher fractions in infants dying from SIDS compared to age-matched control infants.

Design.—We performed a cross-sectional study using high-performance liquid chromatography to measure HbF fractions in newborn cord blood samples. Exposure to selected risk factors for SIDS was assessed through review of medical records.

Participants.—Six hundred thirty-three infants born at Via Christi Regional Medical Center–St Francis Campus, Wichita, Kan, from February 28 through August 5, 1997.

Main Outcome Measure.—Hemoglobin F fractions at birth were compared in newborns exposed and not exposed to selected risk factors associated with increased incidence of SIDS.

Results.—Mean HbF fractions were significantly higher in preterm newborns of mothers who smoked and in term newborns with intrauterine growth restriction, pregnancy weight gain less than or equal to 9 kg, and pregnancy complications associated with reduced placental blood flow. An elevated newborn HbF fraction, defined as 77% or greater, was significantly associated with maternal smoking, maternal anemia, intrauterine growth restriction, and pregnancy complications associated with reduced placental blood flow.

Conclusion.—This study suggests a possible mechanism (HbF) by which previously identified factors may increase the risk of SIDS.
Analysis of 2 Antiapoptotic Factors in Gliomas
Authors: Rodriguez-Pereira C. , Suarez-Peñaranda J. M. , Barros F. , Sobrido M. J. , Vazquez-Salvado M. , Forteza J.
Published: January 2021

Background.—p53 mutations and immunoreactivity have been described in human gliomas. During the past few years, some authors have found bcl-2 overexpression in astrocytomas, although their correlation with histological grade is a matter of disagreement. A relation between bcl-2 overexpression and p53 immunoreactivity has also been suggested.

Objectives.—To analyze the frequency of presentation of bcl-2 and p53, their clinicopathologic implications, and their possible coexpression.

Methods.—We studied p53 and bcl-2 with immunohistochemical and molecular methods in 61 gliomas (including 21 astrocytomas, 9 anaplastic astrocytomas, 29 glioblastomas, 1 oligodendroglioma, and 1 mixed glioma).

Results.—We discovered a high level of bcl-2 overexpression (57%). Overexpression of bcl-2 can be an early event in gliomas tumorigenesis, although no correlation was found with any of the clinicopathologic parameters studied. p53 mutations were present in a small proportion of gliomas (17%). p53 immunoreactivity was present in 34 cases (57%), and it was related to histological grade and a supratentorial location. A high percentage of tumors (26 cases, 42%) presented p53 immunoreactivity without p53 mutations.

Conclusions.—Since there was no relation between bcl-2 overexpression and p53 mutations or p53 immunoreactivity, both factors may not act together in the genesis and evolution of gliomas.
Evaluation of the Candigen Enzyme-Linked Immunosorbent Assay for Quantitative Detection of Candida Species Antigen
Authors: Elsayed Sameer , Fitzgerald Viivi , Massey Viki , Hussain Zafar
Published: January 2021

Objective.—To assess the clinical utility of an enzyme-linked immunosorbent assay method for the quantitative detection of Candida species antigen (Candigen; Biomerica Inc, Newport Beach, Calif) in patients with suspected disseminated candidiasis.

Methods.—Specimens of blood or cerebrospinal fluid from 75 patients with suspected disseminated candidiasis were analyzed by the Candigen test. Results were compared with those obtained by culture and polymerase chain reaction (PCR) analysis.

Results.—Thirty-seven patients had specimens positive for Candida species by either culture or PCR. Of these specimens, 4 were positive by both culture and PCR, 21 were culture positive but PCR negative, and 12 were PCR positive but culture negative. Five specimens were positive by the Candigen test, all of which were PCR positive but culture negative. The sensitivity, specificity, and positive and negative predictive values of the Candigen test compared to culture plus PCR were 13.5%, 100%, 100%, and 54.3%, respectively. Turnaround time for the Candigen test was approximately 3 hours.

Conclusion.—The Candigen test showed excellent specificity and turnaround time, but its poor sensitivity coupled with its inability to provide species information or susceptibility data make its clinical utility questionable.
Verumontanum Mucosal Gland Hyperplasia Is Associated With Atypical Adenomatous Hyperplasia of the Prostate
Authors: Muezzinoglu Bahar , Erdamar Sibel , Chakraborty Subhendu , Wheeler Thomas M.
Published: January 2021

Background.—Verumontanum mucosal gland hyperplasia (VMGH) and atypical adenomatous hyperplasia (AAH) are both small glandular proliferations that are histologically and topographically unique.

Methods.—One hundred ten randomly selected, whole-mount, radical prostatectomy specimens were reviewed to assess independently the normal histology of the prostatic urethra and periurethral area and the association of AAH with other pathologic features, including VMGH. The degree of nodular hyperplasia was evaluated by total prostate weight for comparison purposes.

Results.—Atypical adenomatous hyperplasia was found in 37 cases (33.6%) and was nearly always (32/37) associated with nodules of nodular hyperplasia. Verumontanum mucosal gland hyperplasia was present in 32 cases (29.1%; 21 with AAH, 11 without AAH). There was a significant association between presence of VMGH and AAH (P < .001, Fisher exact test). The degree of nodular hyperplasia was not significantly different between prostates with and without VMGH or AAH.

Conclusions.—These results suggest that AAH and VMGH occur more commonly in prostates when the other is also present.
Low Triglyceride Levels Affect Calculation of Low-Density Lipoprotein Cholesterol Values
Authors: Wang Teh Y. , Haddad Michel , Wang Thomas S.
Published: January 2021

The Friedewald formula for the calculation of low-density lipoprotein cholesterol (LDL-C) values is fairly accurate provided the triglyceride value is less than 400 mg/dL. It is not clear whether the estimation is also valid in the presence of low triglyceride and high cholesterol levels. We describe herein a patient with a low triglyceride value of approximately 50 mg/dL, a high cholesterol level, and a discrepant LDL-C level. The LDL-C level using the Friedewald calculation turned out to be much higher than the LDL-C level using direct measurement. We, therefore, suggest that in the presence of low triglyceride and high cholesterol levels, the LDL-C level should be measured directly instead of using the Friedewald calculation.
Primary Liposarcoma of the Liver
Authors: Nelson Viera , Fernandes Neville F. , Woolf Graham M. , Geller Stephen A. , Petrovic Lydia M.
Published: January 2021

Liposarcoma is a rare mesenchymal malignant tumor, which usually originates in the retroperitoneum and the extremities. Seven cases of primary liposarcoma of the liver have been previously reported. We present the eighth case, which occurred in an adult female patient. Primary liposarcoma of the liver, although extremely rare, must be considered in the differential diagnosis of a hepatic mass that develops in a noncirrhotic liver, especially in patients who are potential candidates for orthotopic liver transplantation. Liposarcoma is an absolute contraindication for liver transplantation.