bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirements for Accreditation by the College of American Pathologists Laboratory Accreditation Program
Authors: Hamlin William B.
Published: January 2021

The College of American Pathologists Laboratory Accreditation Program expects a participant laboratory or laboratory section to be able to demonstrate that it is in compliance with the Standards for Laboratory Accreditation. The program expects laboratories to demonstrate that they are continually taking steps to identify and correct deficient areas and improve performance, in compliance with the Clinical Laboratory Improvement Amendments of 1988 regulatory requirements, particularly those pertaining to proficiency testing performance, and participating as inspectors in the accreditation process.
Health Care Financing Administration/Clinical Laboratory Improvement Amendments of 1988
Authors: Wanamaker Virginia
Published: January 2021

The Health Care Financing Administration has introduced new concepts for the Clinical Laboratory Improvement Amendments of 1988 survey program. Surveyors now look at the laboratory as a whole as opposed to each regulatory requirement independently. This quality assurance approach allows the surveyor to assess the laboratory's ability to provide quality test results as well as identify and correct its own problems. Significant problems in laboratories are more easily identified using this method. Another new concept allows good performing laboratories to go longer between on-site surveys by completing a self-assessment questionnaire on alternate cycles. The Health Care Financing Administration is asking both surveyors and laboratories to evaluate these new approaches. The Health Care Financing Administration continues to work with the Food and Drug Administration through our Memorandum of Understanding to assess Food and Drug Administration requirements in hospitals and laboratories that provide transfusion services. Transfusion-related fatalities must be reported to the Food and Drug Administration and may be investigated by either the Health Care Financing Administration or the Food and Drug Administration. For fatalities needing investigation by both agencies, every effort will be made to conduct these jointly.
Immunohistochemical Profile of Myogenin and MyoD1 Does Not Support Skeletal Muscle Lineage in Alveolar Soft Part Sarcoma
Authors: Gómez JoséA. , Amin Mahul B. , Ro Jae Y. , Linden Michael D. , Lee Min W. , Zarbo Richard J.
Published: January 2021

Background.—The histogenesis of alveolar soft part sarcoma remains elusive. Myogenic origin is favored, although conflicting data on immunohistochemical demonstration of muscle-associated markers exist. Myogenin and MyoD1, transcription factors of the myogenic determination family, have crucial roles in commitment and differentiation of mesenchymal progenitor cells to myogenic lineage and in maintenance of skeletal muscle phenotype. Their immunohistochemical detection is specific in characterization of rhabdomyosarcoma.

Methods.—Antibodies for myogenin, MyoD1, desmin, and muscle-specific actin were employed on a large series of cases (n = 19) of formalin-fixed, paraffin-embedded alveolar soft part sarcoma.

Results.—Minimal scattered nuclear staining was seen with myogenin. All cases had pronounced, nonspecific granular cytoplasmic immunostaining with MyoD1; nuclei were negative. All tumors were negative for desmin and muscle-specific actin. Ultrastructural study in 10 cases failed to reveal features of skeletal muscle differentiation.

Conclusions.—Cytoplasmic staining with MyoD1 in alveolar soft part sarcoma may correspond to cross-reactivity with an undetermined cytoplasmic antigen. The lack of immunostaining with myogenin, MyoD1, desmin, and muscle-specific actin provides evidence against a myogenic origin for alveolar soft part sarcoma.
Histologic Sectioning Produces TUNEL Reactivity
Authors: Sloop Gregory D. , Roa Juan C. , Delgado Alberto G. , Balart John T. , Hines Merrill O. , Hill James M.
Published: January 2021

Objective.—To determine if the DNA strand breaks caused by tissue sectioning result in terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end-labeling (TUNEL) reactivity.

Methods.—The incidence and location of TUNEL-positive nuclei were determined in 5- and 15-μm sections of human stomach. Five- and 15-μm sections of tonsil were stained as a positive control.

Results.—In 5-μm gastric sections, 69% of nuclei were labeled; in 15-μm sections, only 30% were labeled. In the latter sections, almost all labeled nuclei were located at the cut surface of sections. Labeled nuclei did not have apoptotic morphology. Apototic bodies and tingible body macrophages were labeled throughout 15-μm sections of tonsil.

Conclusions.—Tissue sectioning creates TUNEL reactivity. The morphologic findings on routine stains should be considered the gold standard for the detection of apoptosis on tissue sections.
Atypical Cellular Chorangioma
Authors: Mesia Augusto F. , Mo Peter , Ylagan Lourdes R.
Published: January 2021

We describe an unusual, large atypical cellular chorangioma with abundant mitoses and focal necrosis. Other than premature birth, the prenatal and postpartum clinical course was unremarkable for both the mother and baby. Our case and a few similar cases reported in literature suggest that atypical cellular chorangioma is a benign tumor, despite its worrisome histopathologic features.
Assessing Blood Administering Practices
Authors: Shulman Ira A. , Saxena Sunita , Ramer Lois
Published: January 2021

The risk that a red blood cell unit will be associated with an ABO-incompatible transfusion is currently slightly greater than the aggregate risk of acquiring human immunodeficiency virus, human T-cell lymphotropic virus, hepatitis B virus, or hepatitis C virus by transfusion. Since the most common cause for ABO-incompatible transfusion is the failure of transfusionists to properly identify a patient or a blood component before a transfusion, transfusion services are encouraged to evaluate and monitor the processes of dispensing and administering blood. In addition, a proposal of the Health Care Financing Administration of the Department of Health and Human Services would require hospitals to use a data-driven quality assessment and performance improvement program that evaluates the dispensing and administering of blood and that ensures that each blood product and each intended recipient is positively identified before transfusion. The Los Angeles County+University of Southern California Medical Center assesses the blood dispensing and administering process as proposed by the Health Care Financing Administration. During the fourth quarter of 1997, 85 blood transfusions were assessed for compliance with the Los Angeles County+University of Southern California Medical Center policies and procedures: 55 transfusion episodes had no variance from institutional protocol and 30 had one or more variances. Of the transfusions with at least one variance, 16 had one or more variances involving the identification of the patient, the component, or the paperwork. The remaining 14 transfusions had one or more variances involving other criteria (nonidentification items). The most frequent variance was the failure to document vital signs during the first 15 minutes after a transfusion was started or after 50 mL of a component had been transfused. No variances in patient or blood component identification were noted in nursing units whose staff routinely performed self-assessment of blood administering practices. Based on these findings, a corrective action plan was implemented. Follow-up assessments (n = 63) were conducted after 3 months (during the second quarter of 1998). The compliance with the pretransfusion identification protocol improved from 81% to 95%. The most common reason for noncompliance continued to be a lack of checking vital signs. This report demonstrates the value of using a data-driven program that assesses blood administering practices.
Blood Transfusion–Acquired Hemoglobin C
Authors: Suarez Adrian A. , Polski Jacek M. , Grossman Brenda J. , Johnston Marilyn F. M.
Published: January 2021

Unexpected and confusing laboratory test results can occur if a blood sample is inadvertently collected following a blood transfusion. A potential for transfusion-acquired hemoglobinopathy exists because heterozygous individuals show no significant abnormalities during the blood donor screening process. Such spurious results are infrequently reported in the medical literature. We report a case of hemoglobin C passively transferred during a red blood cell transfusion. The proper interpretation in our case was assisted by calculations comparing expected hemoglobin C concentration with the measured value. A review of the literature on transfusion-related preanalytic errors is provided.
Diagnostic Uncertainty Expressed in Prostate Needle Biopsies
Authors: Novis David A. , Zarbo Richard J. , Valenstein Paul A.
Published: January 2021

Objective.—To determine the rate of diagnostic uncertainty in rendering diagnoses on prostate needle biopsies and to examine pathology practice variables that influence that rate.

Design.—Anatomic pathology departments participating in the College of American Pathologists Q-Probes laboratory quality improvement program retrospectively reviewed their last 50 consecutive prostate needle biopsy diagnoses. For each diagnosis, participants provided information concerning patients' prostate-specific antigen levels; number, locations, and laterality of biopsy specimens; number of tissue levels examined; performance of high-molecular-weight cytokeratin immunoperoxidase staining; and acquisition of consultations from general pathologists or experts in prostate pathology. Characteristics of pathology practices included yearly surgical and prostate needle biopsy caseloads, number of pathologists rendering biopsy diagnoses, use of standard descriptive checklists, access to patients' prostate-specific antigen and digital rectal examination results, percentages of prostate needle biopsies routinely submitted for internal consultations, and presence of departmental experts in prostate pathology.

Setting and Participants.—Three hundred thirty-two public and private institutions located in the United States (n = 318), Canada (n = 6), Australia (n = 5), United Kingdom (n = 2), and Guam (n = 1).

Main Outcome Measure.—The rate of diagnostic uncertainty in prostate needle biopsy diagnoses.

Results.—Participants submitted diagnoses on a total of 15 753 prostate needle biopsy cases, of which 33.4% were adenocarcinoma; 55.5% were benign; 3.9% were carcinoma in situ, prostatic intraepithelial neoplasia, or both; and 7.1% were diagnostically uncertain. The median rate of diagnostic uncertainty was 6%, ranging from 0 at the 10th percentile to 14% at the 90th percentile of all participating laboratories. Performing high-molecular-weight cytokeratin immunoperoxidase staining resolved diagnostic uncertainty in 68% of cases in which it was performed, and obtaining intradepartmental and extradepartmental consultations resolved diagnostic uncertainty in 70% to 87% of cases for which they were obtained. Knowledge of patients' prostate-specific antigen results and examining multiple biopsy cores had marginal effects on the rate of uncertainty. Thoroughness of prostate gland sampling and examination of multiple tissue block levels were not associated with the aggregate rate of diagnostic uncertainty. We found no particular pathology departmental practices or institutional demographic characteristics associated with institutional rates of diagnostic uncertainty.

Conclusions.—Use of high-molecular-weight cytokeratin immunoperoxidase staining and obtaining intradepartmental and extradepartmental consultations may be effective in reducing diagnostic uncertainty in prostate biopsies.
Hybrid Carcinomas of Salivary Glands
Authors: Croitoru Claudia M. , Suarez Patricia A. , Luna Mario A.
Published: January 2021

Objective.—To report 4 cases of hybrid carcinoma and to review the literature on these rare neoplasms of the salivary gland.

Methods.—Hematoxylin-eosin–stained, formalin-fixed, paraffin-embedded tissue sections from 3 parotid tumors and 1 palate tumor were examined.

Results.—The cases were classified as adenoid cystic and mucoepidermoid carcinoma, adenoid cystic and epithelial-myoepithelial carcinoma, epithelial-myoepithelial and salivary duct carcinoma, and adenoid cystic and salivary duct carcinoma. All patients were men, 28 to 71 years old; 3 patients presented with parotid mass, and 1 patient presented with palatal mass. One patient presented with facial nerve paralysis and pain. The soft palatal tumor was a slowly growing mass with maxillary sinus involvement at the time of the diagnosis. All patients were treated with surgery and radiotherapy.

Conclusions.—Correct identification of 2 or more neoplastic entities will help assess the aggressiveness and metastatic potential of the tumor and influence the clinical course and treatment.
Tumor-to-Tumor Metastasis to Follicular Variant of Papillary Carcinoma of Thyroid
Authors: Baloch Zubair W. , LiVolsi Virginia A.
Published: January 2021

Objective.—To describe and document tumor-to-tumor metastases in the thyroid gland.

Methods and Results.—In this series we describe 3 cases of tumor-to-tumor metastasis in which the recipient tumor was a follicular variant of papillary thyroid carcinoma. The donor tumors and sites were small cell carcinoma of the lung, neuroendocrine carcinoma probably of pancreatic origin with initial presentation as liver metastasis, and clear cell carcinoma of the kidney with metastasis to liver and pancreas. The donor tumor cells infiltrated the substance of the follicular variant of papillary thyroid carcinoma, the nontumorous thyroid parenchyma, and the lymphovascular spaces. Small cell carcinoma and neuroendocrine carcinoma showed positive reactivity for neuroendocrine markers and were negative for thyroglobulin and calcitonin. The follicular variant of papillary thyroid carcinoma showed positivity with thyroglobulin and cytokeratin 19.

Conclusions.—Although tumor-to-tumor metastases in thyroid gland are exceedingly rare, one should be aware of this phenomenon as the metastatic lesion may simulate a thyroid primary. History of a previous tumor and immunohistochemical stains can be helpful in distinguishing between primary and metastatic thyroid neoplasms.
Carcinoma in Jejunal Pancreatic Heterotopia
Authors: Makhlouf Hala R. , Almeida John L. , Sobin Leslie H.
Published: January 2021

Background.—Although heterotopic pancreas in the gastrointestinal tract is not uncommon, jejunal pancreatic heterotopia is a rare finding, and malignant transformation in such a location is very unusual.

Methods.—We encountered a case of jejunal carcinoma in pancreatic heterotopia and because of its rarity, we reviewed the Armed Forces Institute of Pathology experience as well as the literature. The clinical, histopathologic, and immunohistochemical features were studied.

Results.—In 109 patients diagnosed as having pancreatic heterotopia in the gastrointestinal tract between 1970 and 1997 at the Armed Forces Institute of Pathology, 67 cases (62%) occurred in the stomach, 42 (38%) in the small intestine, and none in the large intestine. We found 2 patients with adenocarcinoma arising in pancreatic heterotopia. The 2 cases arose in the jejunum. One was of the ductal type, while the other was an acinar cell carcinoma with focal ductular differentiation. In both cases the nontumoral pancreatic tissue contained ducts, acini, and islets. Review of the literature yielded 26 reports of 28 cases of carcinoma arising in heterotopic pancreas; of these, 18 were well documented. Only 1 occurred in the jejunum, and none was of the acinar type.

Conclusions.—Carcinoma in pancreatic heterotopia is rare, and acinar cell carcinoma in pancreatic heterotopia is extremely rare. Recognition of carcinoma in pancreatic heterotopia is important to prevent its misinterpretation as a metastatic tumor.
Diagnostic Accuracy and Clinical Utility of Endoscopic Bile Duct Brushing in the Evaluation of Biliary Strictures
Authors: Trent Vincent , Khurana Kamal K. , Pisharodi Latha R.
Published: January 2021

Pathologic evidence of malignancy in biliary strictures is useful in the preoperative setting because it helps define therapeutic planning and prognosis. The purpose of this study was to assess the diagnostic accuracy and clinical utility of endoscopic bile duct brushings in the evaluation of bile duct strictures. We retrospectively evaluated 34 endoscopic biliary brushings derived from 31 patients with bile duct strictures. Relevant clinical and follow-up data were collected. Histologic specimens were reviewed in patients undergoing subsequent biopsies. Patients included 18 men and 13 women with an age range of 25 to 79 years (mean, 52 years). All patients had histologic and/or clinical follow-up. Cytologic diagnosis included cholangiocarcinoma (14.7%), suspicious for cholangiocarcinoma (5.9%), atypical hyperplasia (17.6%), and negative for malignancy (61.7%). All positive diagnoses were confirmed by histologic testing (false-positive rate, 0%). The cases that were suspicious for cholangiocarcinoma and the 5 atypical hyperplasia cases were also subsequently diagnosed as cholangiocarcinoma by biopsy. One atypical case was diagnosed as pancreatic carcinoma. All 21 negative cases were confirmed by biopsies (15) and clinical follow-up (6) (false-negative rate, 20%). Endoscopic bile duct brushing is diagnostically accurate and hence clinically useful in the management of patients with bile duct strictures. Atypical hyperplasias may contribute to diagnostic pitfalls leading to false-positive and false-negative diagnoses.
Lymphoepithelioma-like Carcinoma of the Colon in a Patient With Hereditary Nonpolyposis Colorectal Cancer
Authors: De Petris Giovanni , Lev Robert , Quirk Daniel M. , Ferbend Paul R. , Butmarc Janet R. , Elenitoba-Johnson Kojo
Published: January 2021

Tumors with features similar to those of nasopharyngeal carcinoma, so-called lymphoepithelioma-like carcinomas, have been described in several organs but are extremely rare in the colon. We describe a patient with a family history consistent with hereditary nonpolyposis colorectal cancer who had 3 malignant lesions in the right colon, namely, a mucinous cancer, a lymphoepithelioma-like carcinoma, and a well-differentiated adenocarcinoma with prominent lymphoid stroma. To the best of our knowledge, lymphoepithelioma-like carcinoma has not been described previously in hereditary nonpolyposis colorectal cancer.
Diagnosis of Primary Fibrosarcoma of the Lung by Fine-Needle Aspiration and Core Biopsy
Authors: Logrono Roberto , Filipowicz Ewa A. , Eyzaguirre Eduardo J. , Sawh Ravindranauth N.
Published: January 2021

Primary pulmonary sarcomas are uncommon neoplasms. Primary fibrosarcoma of the lung is extremely rare, and only 53 cases have been documented in the literature to date. To our knowledge, the diagnosis of primary lung fibrosarcoma by fine-needle aspiration cytology has never been reported. We report a case of pulmonary fibrosarcoma diagnosed by fine-needle aspiration cytology and core biopsy. The neoplasm consisted of interweaving fascicles of minimally atypical spindle cells with slender nuclei and scant cytoplasm. Positive immunohistochemistry for vimentin along with nonreactivity of tumor cells for keratin, S100 protein, desmin, α-smooth muscle actin, and CD34 supported the the diagnosis. The diagnosis was later confirmed by histologic and ultrastructural findings following lobectomy. A meticulous clinical search for a possible primary neoplasm elsewhere was unsuccessful, and lung was established as the primary site. Fine-needle aspiration cytology and core biopsy are reliable methods for establishing a diagnosis of fibrosarcoma.
BK Virus Renal Infection in a Patient With the Acquired Immunodeficiency Syndrome
Authors: Nebuloni Manuela , Tosoni Antonella , Boldorini Renzo , Monga Guido , Carsana Luca , Bonetto Sara , Abeli Clara , Caldarelli Rita , Vago Luca , Costanzi Giulio
Published: January 2021

Background.—We describe herein a patient with the acquired immunodeficiency syndrome and renal failure due to biopsy-proven BK virus (BKV) infection. Three months after the diagnosis of the renal viral infection, his condition remained unchanged. Although BKV has previously been shown to be associated with ureteral stenosis and renal damage in renal transplant patients, to our knowledge, the literature contains only 3 cases describing the presence of BKV lesions in the kidneys of immunosuppressed patients who had not undergone transplantation.

Methods.—The presence of BKV infection was demonstrated by means of histology, immunohistochemistry with polyclonal anti-SV40 antibody, immunoelectron microscopy, polymerase chain reaction, and enzymatic cleavage with BamHI.

Results.—Histologic examination revealed interstitial inflammatory infiltrates and tubules with enlarged and eosinophilic nuclei.

Conclusions.—The high frequency of latent BKV infection and its reactivation during immunosuppression suggest that the possibility of its involvement in renal damage should be considered in immunocompromised patients.
Continuous Quality Improvement for Point-of-Care Testing Using Background Monitoring of Duplicate Specimens
Authors: Kilgore Meredith L. , Steindel Steven J. , Smith John A.
Published: January 2021

Context.—Despite compliance with quality control standards, concerns remain as to the accuracy and reliability of point-of-care testing.

Objective.—To assess a practical method for quality improvement using the context in which point-of-care testing is done.

Design.—Quality measures for point-of-care testing, making use of natural duplication of results obtained by other testing methods, were used to monitor testing quality and evaluate quality improvement interventions.

Setting.—Five adult intensive care units (total of 88 beds) in a large academic medical center, using point-of-care testing for blood gases, electrolytes, and hematocrit levels.

Participants.—Nurses performing bedside testing and laboratory personnel assigned the responsibility for supervising their performance.

Interventions.—Quality of testing was monitored continuously, and, where problems were identified, training and support interventions implemented, and their effects evaluated.

Main Outcome Measures.—Improvement in correlation coefficients and regression parameters of point-of-care hematocrit and potassium testing results compared with contemporaneous results from the core laboratory.

Results.—The initial survey found point-of-care potassium levels were tightly correlated with core laboratory results (r = 0.958). Baseline correlation coefficients and regression parameters for point-of-care hematocrit levels compared with core laboratory values varied widely from unit to unit. The intensive care units with the highest variances of bedside vs core laboratory testing received targeted interventions. Follow-up yielded evidence of dramatic improvement; 1 unit experienced an increase in correlation from 0.50 to 0.95.

Conclusions.—The findings suggest that, when point-of-care testing is highly dependent on operator technique, targeted interventions can resolve problems and provide reliable results at the bedside.
Coinfection of Visceral Leishmaniasis and Mycobacterium in a Patient With Acquired Immunodeficiency Syndrome
Authors: Wang Jun , Vanley Christopher , Miyamoto Eric , Turner Jerrold A. , Peng Shi-Kaung
Published: January 2021

We report a case of coinfection of visceral leishmaniasis and Mycobacterium avium-intracellulare in the same lesions in the small bowel and bone marrow of a 33-year-old man with acquired immunodeficiency syndrome who complained of abdominal pain and chronic diarrhea. The duodenal mucosa and bone marrow biopsy specimens showed numerous foamy macrophages packed with two forms of microorganisms that were identified histologically and ultrastructurally as Leishmania and Mycobacterium species. Visceral leishmaniasis is rarely suspected in patients residing in nonendemic countries including the United States. It should be included in the differential diagnosis for opportunistic infection in patients with acquired immunodeficiency syndrome. An appropriate travel history is important. To our knowledge, this is the first reported case showing coinfection of visceral leishmaniasis and Mycobacterium avium-intracelluulare in the same lesion in a patient with acquired immunodeficiency syndrome.
Benign Fibroepithelial Polyps of the Renal Pelvis
Authors: Nowak Michael A. , Marzich Christine S. , Scheetz Kevin L. , McElroy John B.
Published: January 2021

Benign fibroepithelial polyps of the renal pelvis are rare. Although many ureteral fibroepithelial polyps have been reported, there are, to our knowledge, only 20+ reported cases in the renal pelvis.1–9,11–22 We report herein the clinical and pathologic features of fibroepithelial polyp of the renal pelvis and provide a detailed review of the literature.
A Simplified Method for Postmortem Coronary Angiography Using Gastrograffin
Authors: Smith Michael , Trummel Donald E. , Dolz Mark , Cina Stephen J.
Published: January 2021

Objective.—To assess the adequacy of perfusion of the heart at autopsy with a gastrograffin and dye mixture to obtain rapid postmortem angiograms while simultaneously documenting the vascular distribution of the myocardium.

Background.—Postmortem coronary angiography is occasionally used in the evaluation of suspected cardiac deaths. Angiography provides legal documentation and can serve to guide subsequent cardiac dissection. Multiple techniques have been suggested in the literature for coronary angiography using infusion of radio-opaque silicone or gelatin. These techniques are cumbersome and require equipment generally not available in autopsy suites.

Methods.—Following removal of the heart, a mixture of gastrograffin and colored dyes is injected into each coronary artery via a syringe. The coronary arteries are ligated and radiographs are obtained. After fixation, the heart is dissected in the usual manner.

Results.—Adequate postmortem coronary angiograms are routinely obtained with this method. The coronary arterial distribution within the myocardium is easily documented at both the gross and microscopic levels because of the presence of differential coloration.

Conclusions.—The aforementioned technique using a gastrograffin and dye mixture provides a simplified approach to postmortem angiography. The novelty of the procedure stems from the low cost, ease of implementation, dual ability to assess vascular anatomy radiologically (gastrograffin), and gross distribution and histologic findings of dependent tissue using the light microscope (colored dye). This technique is inexpensive, rapid, and easily used, making it more suitable for general hospital practice and medical examiners' offices than previously described methods.
Molecular Pathology and Clinicopathologic Features of Penile Tumors
Authors: Lam King Y. , Chan Kwok W.
Published: January 2021

Objectives.—To examine the histologic features of p21 in penile tumors and to determine the role of p21 and p53 in the pathogenesis of this group of tumors.

Methods.—The clinicopathologic features of 87 patients with penile tumors were studied. The expression of p53 and p21 proteins in 49 cases was investigated by immunohistochemistry.

Results.—Of the 87 tumors studied, 84 represented primary penile tumors (72 malignant and 12 benign) and 3 represented secondary tumors (2 from bladder, 1 from nasopharynx). The primary malignant penile tumors included 66 surface carcinomas with squamous differentiation (92%), 3 cases of Paget disease (4%), 1 case of Bowen disease (1%), and 2 penile urethral squamous cell carcinomas (3%). The former group was subdivided into squamous cell carcinoma (n = 50), verrucous carcinoma (n = 8), basaloid squamous cell carcinoma (n = 3), adenoid squamous cell carcinoma (n = 3), spindle cell carcinoma (n = 1), and adenosquamous carcinoma (n = 1). The benign tumors were squamous cell papillomas (n = 10) and fibromatoses (n = 2). Expression of p21 and p53 was noted in 40% and 89%, respectively, of the 47 patients with primary surface penile carcinoma with squamous differentiation. Positive p21 and p53 expression was also seen in 2 cases of Paget disease. Staining for p21 was often weak and was found in the suprabasal region of carcinomas with squamous differentiation, while p53 expression was seen in the basal region of squamous cell carcinomas. Preinvasive lesions also showed p21 and p53 expression. An inverse correlation between p53 and p21 expression (p53+/p21− or p53−/p21+) was noted in half of the squamous cell carcinomas, 4 of 5 verrucous carcinomas, 2 of 3 basaloid squamous cell carcinomas, and in 1 spindle cell carcinoma. The other cases did not show this correlation.

Conclusions.—Penile tumors had different histologic variants and p21/p53 expression patterns. Expression of p21 did play a role in some tumors and could be dependent or independent of p53 expression.
Comparison of Glycoprotein Expression Between Ovarian and Colon Adenocarcinomas
Authors: Multhaupt Hinke A. B. , Arenas-Elliott Carmen P. , Warhol Michael J.
Published: January 2021

Objective.—Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens.

Design.—We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas.

Results.—CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both primary and metastatic lesions. Mucinous ovarian adenocarcinomas differed in that they express carcinoembryonic antigen and cytokeratins 7 and 20 and weakly express CA125. The other glycoprotein antigens were equally expressed by ovarian and colonic adenocarcinomas and therefore were of no use in distinguishing between these 2 entities.

Conclusion.—A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot be distinguished from colonic adenocarcinomas using immunohistochemistry.
Hoechst 33342 Induces Apoptosis in HL-60 Cells and Inhibits Topoisomerase I In Vivo
Authors: Zhang Xinbo , Chen Jenn , Davis Bruce , Kiechle Frederick
Published: January 2021

Context.—Bisbenzimides (Hoechst 33342 and Hoechst 33258) are cell-permeable, adenine-thymine–specific dyes that bind to the minor groove of DNA and stain DNA. Hoechst 33342 induces apoptosis in BC3H-1 myocytes and hepatoma cells.

Objective.—To determine if Hoechst 33342 or Hoechst 33258 induces apoptosis in human promyelocytic leukemia cells (HL-60) and inhibits topoisomerase I activity.

Design.—A variety of methods were used to detect apoptosis: cell viability (trypan blue exclusion), nuclear fluorescence staining (Hoechst 33342 or Hoechst 33258 stained for 10 minutes), flow cytometric quantitation of annexin binding to phosphatidylserine, and DNA fragmentation (agarose gel electrophoresis). Topoisomerase I activity was determined by a plasmid unwinding assay.

Setting.—A large teaching hospital and research laboratories.

Patients.—None.

Intervention.—None.

Main Outcome Measurements.—Apoptosis is characterized by decreased cell viability, condensation of nuclear chromatin, increased phosphatidylserine translocation, and DNA fragmentation into oligonucleosomes composed of multiples of 180 to 200 base pairs. Inhibition of endogenous nuclear topoisomerase I is detected by the absence of plasmid unwinding from a tightly coiled to relaxed form.

Results.—Hoechst 33342, but not Hoechst 33258, induced apoptosis in the HL-60 cells in a time- and dose-dependent manner. Endogenous nuclear topoisomerase I activity in HL-60 cells was inhibited by treatment with Hoechst 33342 but not Hoechst 33258.

Conclusion.—Hoechst 33342–induced HL-60 cell apoptosis may be related to the dye's inhibition of topoisomerase I activity.
An Optimized Strategy for Choosing the Number of Platelet Concentrates to Pool
Authors: Hoeltge Gerald A. , Shah Amrik , Miller John P.
Published: January 2021

Context.—The number of platelet concentrates (PCs) pooled per dose varies widely. The number should be based on quality control statistics.

Objective.—To determine the optimal number of PCs per pool that will achieve a target dose.

Design.—The population statistics of PC cell counts were obtained from routine quality control records. A target value of 3.00 × 1011 cells was chosen. A theoretical model to predict the probability of achieving this target cell count was developed.

Main Outcome Measures.—The calculated probability was tested in a Monte Carlo simulation.

Results.—The mean of a sequential series of 100 PC counts (obtained from routine quality control records) was 9.08 × 1010, and the standard deviation was 2.70 × 1010. Platelet loss during pooling was measured at 8.3%, so that the pooling of 3.27 × 1011 cells is required to deliver a dose of 3.00 × 1011 cells. The pooling of 4 PCs from this data set predicts an average pool cell count of 3.63 ± 2.30 × 1011. Using standard tables for normal distribution, the probability of achieving a minimal pool dose of 3.00 × 1011 cells is estimated to be greater than 0.76. Similarly, the probability of achieving the target value by pooling 5 PCs is greater than 0.99. In a Monte Carlo simulation selecting 4 PCs, 76.5% of the trials were successful, and for 5 PCs, 99.5% were successful (estimated P values of .77 and .99, respectively).

Conclusion.—Five PCs per pool are necessary and sufficient to achieve the chosen target value given the cell count characteristics of our PC supply.
Multifocal Granular Cell Tumor of the Esophagus and Proximal Stomach With Infiltrative Pattern
Authors: David Odile , Jakate Shriram
Published: January 2021

The granular cell tumor is a solitary painless nodule that arises most commonly on the skin or the tongue. The vast majority are benign. Approximately 5% to 9% of granular cell tumors have been reported in the gastrointestinal tract, most commonly in the esophagus. We report a case of a 45-year-old African American woman with multifocal granular cell tumors of the esophagus and proximal stomach. Two lesions within the distal esophagus and proximal stomach were characteristic nodular granular cell tumors. Within the mid esophagus there was poorly defined transmural involvement by benign-appearing granular cells. This pattern of infiltration by benign cells is uncharacteristic. A review of the literature with emphasis on the determination of malignancy is also presented.
Muscular Dystrophy
Authors: Hoffman Eric P.
Published: January 2021

The application of cloned genes and their protein products to molecular diagnostics has been an increasingly important area of pathology. The first gene to be identified by positional cloning was the Duchenne muscular dystrophy gene, mutations of which cause one of the most common and most devastating human inherited conditions. The identification of the responsible gene and the encoded dystrophin protein has resulted in a large series of studies concerning the other components of the membrane cytoskeleton of myofibers and their involvement in different forms of muscular dystrophy. Through the study of patients deficient in specific components of the muscle fiber, much is being learned about normal myofiber structure and function and dysfunction in disease states. A new frontier is the application of the normal genes and proteins toward patient therapeutics (gene therapy). Although highly experimental, delivery of therapeutic genes promises to become an important medical practice.
Impact of Molecular (DNA) Testing on Determination of Parentage
Authors: Polesky Herbert F.
Published: January 2021

Objective.—To examine changes in parentage testing practices since the introduction of DNA polymorphisms.

Methods.—Comparison of data from American Association of Blood Banks (AABB) annual questionnaires and the responses of participants to AABB–College of American Pathologists proficiency test panels.

Results.—DNA polymorphisms have led to a complete change in the technical methods used by parentage testing laboratories.

Conclusions.—The widespread use of DNA methods has increased the power of the information routinely provided to the courts in cases of disputed paternity, to agencies needing information about relatedness, and to the individuals who are tested.
Financial Determinants of Outcomes in Molecular Testing
Authors: Ross Jeffrey S.
Published: January 2021

For the benefits of molecular pathology to outweigh its inherent costs, testing procedures must be integrated into total disease assessment to realize the true financial impact. Major financial benefits are achievable from molecular testing because the tests reduce the use of less sensitive and less specific tests, unnecessary diagnostic procedures, and ineffective therapies. In this review, the financial determinants of outcomes for molecular-based testing for disease predisposition, screening, early detection, and directed therapy are presented.
Implementation of a Practical Digital Imaging System for Routine Gross Photography in an Autopsy Environment
Authors: Belanger Arthur J. , Lopes Antonio E. , Sinard John H.
Published: January 2021

Background.—The autopsy environment places stringent requirements on a digital imaging system. These requirements must be addressed if the system is to be functional, easy to use, and reliable.

Design.—After clearly defining the requirements for such a system, we implemented routine digital imaging in a busy academic autopsy suite.

Results.—The new technology was immediately accepted by both the resident staff and the technical staff. Although a 35-mm camera was always available for traditional photography, it was rarely used. An interesting side effect of implementing digital imaging was a nearly twofold increase in the number of images taken per autopsy case. The requirements, features, and utility of a digital imaging system are discussed.

Conclusion.—Digital imaging in an autopsy environment can be both practical and cost-effective. It provides many advantages over traditional 35-mm photography and can be the first step toward numerous additional improved services.
Atypical Epithelial Cells and Specimen Adequacy
Authors: Davey Diane D. , Woodhouse Sherry , Styer Patricia , Stastny Janet , Mody Dina
Published: January 2021

Context.—The Bethesda System for reporting cervical/vaginal cytologic diagnoses introduced terminology for atypical squamous and glandular cells and categories for specimen adequacy.

Objectives.—To analyze current laboratory reporting practices and compare trends to previous surveys.

Design.—Questionnaire surveys were mailed to 2000 laboratories in 1996 and 1997.

Participants.—Laboratories enrolled in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.

Main Outcome Measures.—Laboratory policies, criteria, and reporting rates for Bethesda System categories.

Results.—The 1996 specimen adequacy survey had 1166 respondents, and 768 laboratories returned the 1997 questionnaire focusing on atypical squamous cells of undetermined significance (ASCUS) and glandular cells of undetermined significance (AGUS). Nearly all laboratories (92%) routinely reported specimen adequacy, an increase from the 66% rate in 1991. The median rate for unsatisfactory specimens was 0.5% (mean 0.95%), and the median rate for the satisfactory but limited category was 5.8% (mean 9.3%). The Bethesda criteria for designating a specimen unsatisfactory were used by more than 90% of laboratories. Nearly all laboratories (97%) used the term ASCUS in 1997, and more than 80% of laboratories used the Bethesda criteria for this category. Median reporting rates for epithelial abnormalities were as follows: ASCUS, 4.5%; AGUS, 0.3%; low-grade squamous intraepithelial lesion (SIL), 1.6%; and high-grade SIL, 0.5%. The median ASCUS/SIL ratio was 2.0, with 80% of laboratories reporting ratios between 0.64 and 4.23. The median ASCUS rate and ASCUS/SIL ratio were higher than 1993 survey results. Nearly all laboratories attempted follow-up studies on patients with abnormal cytology results, and midsized laboratories achieved the highest rates of follow-up. Median rates of abnormalities following an ASCUS or AGUS diagnosis were 20% and 15%, respectively. Laboratory respondents commonly used written recommendations in ASCUS/AGUS reports.

Conclusions.—Most laboratories that responded to the surveys had adopted Bethesda terminology and criteria for specimen adequacy and ASCUS/AGUS. Reporting rates for SIL and adequacy categories have remained stable, but median ASCUS rates and ASCUS/SIL ratios are higher than in 1993. The AGUS category is reported infrequently, but can be associated with significant pathology.
Role for Activation of Matrix Metalloproteinases in the Pathogenesis of Pulmonary Lymphangioleiomyomatosis
Authors: Matsui Kazuhiro , Takeda Kazuyo , Yu Zu-Xi , Travis William D. , Moss Joel , Ferrans Victor J.
Published: January 2021

Background.—Matrix metalloproteinases (MMPs) have been shown to be involved in the pathogenesis of the destructive pulmonary lesions in patients with lymphangioleiomyomatosis (LAM); in the present report, the activation of these enzymes is examined.

Objective.—To evaluate the role of MMPs and their activating enzymes, immunohistochemical and confocalmicroscopic techniques were used to localize α-smooth muscle actin (α-SMA), HMB-45, proliferating cell nuclear antigen (PCNA), MMP-2, membrane-type 1 MMP (MT1-MMP), MT2-MMP, and MT3-MMP in lung tissues from 10 women with LAM. Tissue samples were obtained from 5 patients before treatment and in 5 patients after hormone treatment (progesterone and/or tamoxifen citrate).

Results.—Staining for α-SMA and MMP-2 was present in all the abnormal smooth muscle cells (LAM cells) in both groups. The percentages of PCNA-, MMP-2–, or MT1-MMP–positive LAM cells were much higher in the untreated group than in the treated group, whereas the percentages of HMB-45–reactive LAM cells were similar in both groups. The reactions for MT1-MMP and PCNA were preferentially localized in small spindle-shaped LAM cells; the reaction for HMB-45 was found in large epithelioid LAM cells. Many of the PCNA-positive cells were also positive for MT1-MMP. Staining for MT2-MMP and MT3-MMP was negative.

Conclusions.—This study demonstrates an association between cellular proliferation and the presence of MT1-MMP in LAM cells. The activation of MMP-2 by MT1-MMP may play an important role in the destruction of lung tissue in this disorder.
Intraductal Papillary Tumors of the Major Salivary Glands
Authors: Nagao Toshitaka , Sugano Isamu , Matsuzaki Osamu , Hara Hitoshi , Kondo Yoichiro , Nagao Koichi
Published: January 2021

Intraductal papilloma is an extremely rare benign salivary gland tumor that occurs most commonly in the minor salivary glands. To our knowledge, a malignant counterpart of intraductal papilloma has not been described previously. We report one case each of benign and malignant intraductal papillary tumors. The benign tumor occurred in the sublingual gland and was a typical example of intraductal papilloma, with the exception that we found no previously published reports of this type of tumor in this location. The other patient had a left parotid gland tumor that was architecturally similar to the intraductal papilloma, with the addition of cytologic atypia, intraductal extension, microinvasion, and lymph node metastases. This tumor was diagnosed as intraductal papillary adenocarcinoma with an invasive component. Both patients were alive and well without evidence of recurrence 2 years and 6 months (case 1) and 6 years (case 2) after surgery. Immunohistochemical examination revealed that the tumor cells resembled duct luminal cells in both cases. The 2 tumors had different immunoreactivities for carcinoembryonic antigen, p53, and Ki-67. The malignant counterpart of intraductal papilloma should be considered in the differential diagnosis of salivary gland tumors with a predominantly papillary structure, even though this tumor is extremely rare.
Primary Neuroendocrine Small Cell Carcinomaof the Breast
Authors: Samli Billur , Celik Selma , Evrensel Turkkan , Orhan Bulent , Tasdelen Ismet
Published: January 2021

A 60-year-old Turkish woman presented with a left breast mass, which was considered for neoadjuvant chemotherapy. By the end of the treatment cycles, the tumor had decreased in size, and the patient underwent modified radical mastectomy with axillary lymph node dissection. Pathologic examination of the tumor revealed a small cell carcinoma with neuroendocrine features confirmed by immunohistochemical stains. Multiple axillary lymph nodes were involved by metastatic small cell carcinoma carrying the same morphologic characteristics noted in the primary breast tumor. We hereby present this case as a primary neuroendocrine small cell carcinoma of the breast. This entity occurs very rarely in the breast, and fewer than a dozen cases have been reported in the literature. Extrapulmonary small cell carcinoma of the breast is reportedly a very aggressive tumor for which no consensus for treatment has yet been drawn.
Leiomyoma of the Male Urethra
Authors: Mira Jose L. , Fan Guang
Published: January 2021

We describe the case of a 48-year-old quadriplegic black man with history of C4-C5 cervical spine and cord injury secondary to a fall, who presented to the University of Cincinnati Medical Center Urology Service with obstructive symptoms at urination. A bulbous urethral stricture was diagnosed and subsequently resected with primary urethral reanastomosis. On pathologic examination, the surgical specimen contained an epithelioid leiomyoma at the site of the urethral stricture. Although leiomyomas of the female urethra are relatively common, we identified only 2 previously reported cases of leiomyomas of the male urethra in the English-language medical literature. To the best of our knowledge, we describe the third case of leiomyoma of the male urethra, the first of the epithelioid type.