bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability in Cytologic-Histologic Correlation Practices and Implications for Patient Safety
Authors: Vrbin Colleen M. , Grzybicki Dana M. , Sue Zaleski M. , Raab Stephen S.
Published: February 2021

Context.—The Clinical Laboratory Improvement Amendments of 1988 require that laboratories perform cytologic-histologic correlation, although the optimal methods and the value of performing correlation have not been determined.

Objective.—To determine the similarities and differences in how laboratories perform cytologic-histologic correlation.

Design.—One hundred sixty-two American laboratories were sent a letter requesting copies of the materials they used in the cytologic-histologic correlation process. The returned materials were classified into the categories of forms, logs, and tally sheets. A checklist (derived from the College of American Pathologists Laboratory Accreditation Cytopathology Checklist) was developed to classify the “minimum expected” (15) and “additional” data points that laboratories collected when they performed a correlation.

Participants.—American pathology laboratories.

Main Outcome Measures.—Measures were percentage of laboratories that recorded minimum expected and additional data points and the frequency with which specific minimum expected data points were recorded.

Results.—The response frequency was 32.1%, and a total of 84 cytologic-histologic correlation materials were obtained. The only minimum expected variables recorded on forms or logs by more than 50% of laboratories were cytology case number, sign-out cytology diagnosis, surgical pathology case number, and sign-out surgical pathology diagnosis. Nine (17.3%) laboratories did not record data on forms, logs, or tally sheets. The mean number of minimum expected and additional variables recorded on forms was 6.5 and 8.7, respectively.

Conclusions.—Laboratories record data from the cytologic-histologic correlation process in a number of ways, indicating the lack of standardization of the data collection process.
Expression of the Intestinal Marker Cdx2 in Secondary Adenocarcinomas of the Colorectum
Authors: Groisman Gabriel M. , Bernheim Joelle , Halpern Marisa , Brazowsky Eli , Meir Alona
Published: February 2021

Context.—Secondary adenocarcinomas of the large bowel can closely mimic primary tumors. The differentiation of secondary from primary adenocarcinomas of the colorectum, however, is important because their clinical management and prognosis are different. Immunostaining with the nuclear transcription factor Cdx2, expressed in normal intestinal epithelia and colorectal adenocarcinomas, could be of potential diagnostic use.

Objective.—To investigate the diagnostic value of Cdx2 immunoexpression in distinguishing primary from common forms of secondary colorectal adenocarcinomas.

Design.—Cdx2 immunoexpression was analyzed in 20 primary colorectal adenocarcinomas and in 34 secondary colorectal adenocarcinomas and their corresponding primary tumors. All secondary tumors were diagnosed through endoscopic biopsies and included 8 cases of ovarian (4 serous, 2 mucinous, and 2 endometrioid), 6 of mammary (4 lobular and 2 ductal), 4 of gastric (2 intestinal and 2 diffuse), 4 of pulmonary, 4 of pancreatic (ductal), 3 of prostatic, 3 of colorectal, and 2 of endometrial origin.

Results.—Cdx2 was expressed in normal colorectal epithelium, in primary colorectal adenocarcinomas (20/20 cases), in secondary adenocarcinomas of colorectal (3/3) and gastric (3/4) origin, and in metastatic ovarian mucinous adenocarcinomas (2/2). In contrast, no Cdx2 immunoreactivity was observed in secondary colorectal tumors of ovarian (serous and endometrioid), mammary, pancreatic, pulmonary, prostatic, and endometrial origin.

Conclusion.—Cdx2 immunostaining may be useful in discriminating primary colorectal carcinomas from frequent types of secondary colorectal adenocarcinomas of nongastrointestinal origin. We suggest including Cdx2 in any antibody panel put together to distinguish between primary and secondary epithelial colorectal malignancies.
The Unique Simultaneous Occurrence of Granular Cell Tumor, Gastrointestinal Stromal Tumor, and Gastric Adenocarcinoma
Authors: Sailors Joseph L. , French Samuel W.
Published: February 2021

Granular cell tumors are generally benign oncocytoid lesions of schwannian origin that are often incidental findings in many locations. Gastrointestinal stromal tumors occur in older adults and express the c-Kit protein (CD117). Both of these tumors have been described in association with many other entities; however, they have never been reported to occur jointly. This report is prompted by the simultaneous appearance of 2 granular cell tumors, a gastrointestinal stromal tumor, and a gastric adenocarcinoma in a 65-year-old woman with a history of breast carcinoma and granular cell tumor. To our knowledge, this is the first case report of these tumors occurring simultaneously.
A Pseudoepidermoid Cyst Arising From Exuberant Squamous Metaplasia of the Gallbladder
Authors: Teo Clarence Hai Yi , Leow Chon Kar , Chang Satina A.
Published: February 2021

Squamous lesions of the gallbladder are uncommon. We report a case of a pseudoepidermoid cyst in a middle-aged woman arising on a background of chronic cholecystitis and cholelithiasis, which induced exuberant squamous metaplasia of the entire gallbladder mucosa, clinically mimicking a gallbladder tumor. To our knowledge, this is the first such reported case in the English literature.
Verucciform Xanthoma of the Penis Not Associated With Human Papillomavirus Infection
Authors: Erşahin Çağatay , Szpaderska Anna M. , Foreman Kimberly , Yong Sherri
Published: February 2021

Verruciform xanthoma (VX) is a rare lesion with a predilection for oral mucosa. Only 16 cases of VX of the penis have been reported. Histologically, VX lesions in different locations are identical; however, the etiology is controversial. Previous studies have reported the presence of human papillomavirus (HPV) in VX of the skin. The purpose of this study was to determine whether HPV is a causative agent in this rare case of VX of the penis. Microscopically, the lesion demonstrated prominent verrucoid squamous hyperplasia with hyperkeratosis, parakeratosis, and acanthosis. Histiocytes, a hallmark of VX, were identified in the elongated dermal papillae. Nested polymerase chain reaction was performed on the DNA with the commonly used primer sets MY9/MY11 and GP5+/GP6+, which identify more than 40 HPV types. The results failed to identify HPV DNA in the sample, although HPV could be readily detected in genomic DNA extracted from paraffin-embedded condyloma acuminatum, a known HPV-associated lesion. Additionally, we tested a VX lesion of the palate for HPV DNA and obtained negative results. Our results indicate that VX can arise without HPV infection and suggest other possible origins may be involved.
Intraductal Papillary Mucinous Adenoma That Arises From Pancreatic Heterotopia Within a Meckel Diverticulum
Authors: Cates Justin M. M. , Williams Timothy L. , Suriawinata Arief A.
Published: February 2021

Neoplasia is an unusual complication of Meckel diverticulum. Most tumors of Meckel diverticulum are neuroendocrine or mesenchymal in origin. Adenocarcinomas represent a minority of the tumors that arise in Meckel diverticulum and are generally thought to develop from either endogenous small intestinal epithelium or heterotopic gastric epithelium. Despite the presence of ectopic pancreas in a small fraction of Meckel diverticula, convincing evidence of tumors that arise from heterotopic pancreatic exocrine tissue has not been described in this setting. Intraductal papillary mucinous neoplasms are relatively uncommon tumors of pancreatic ductal epithelial cells that line the main pancreatic duct or its major side branches. We present an unusual case of an intraductal papillary mucinous neoplasm that arose in a heterotopic pancreas within a Meckel diverticulum.
Periurethral Carcinosarcoma: A Report of 2 Cases With a Review of the Literature
Authors: Jayamohan Yasodah , Urs Latha , Rowland Randall G. , Woolums Steve , Lele Subodh M.
Published: February 2021

Carcinosarcomas are rare, aggressive tumors that can arise in various sites of the body, especially the genitourinary system. In this system, the most common location for the tumor is the uterus in the female and the urinary bladder in the male. To our knowledge, only 2 cases with a periurethral location for this tumor have been previously described in the English literature. We describe 2 additional cases in this location, one in either sex, with a review of the relevant literature.
Identification Errors Involving Clinical Laboratories: A College of American Pathologists Q-Probes Study of Patient and Specimen Identification Errors at 120 Institutions
Authors: Valenstein Paul N. , Raab Stephen S. , Walsh Molly K.
Published: February 2021

Context.—Misidentified laboratory specimens may cause patient injury, but their frequency in general laboratory practice is unknown.

Objectives.—To determine (1) the frequency of identification errors detected before and after result verification, (2) the frequency of adverse patient events due to specimen misidentification, and (3) factors associated with lower error rates and better detection of errors.

Design.—One hundred twenty clinical laboratories provided information about identification errors during 5 weeks.

Results.—In aggregate, 85% of errors were detected before results were released; one quarter of laboratories identified more than 95% of errors before result verification. The overall rate of patient identification errors involving released results was 55 errors per 1 000 000 billable tests. A total of 345 adverse events were reported. Most of the adverse events caused material inconvenience to the patients but did not result in any permanent harm. On average, adverse events resulted from 1 of every 18 identification errors. Extrapolating the adverse event rate observed in this study to all United States hospital-based laboratories suggests that more than 160 000 adverse events per year result from misidentification of patients' laboratory specimens.

Conclusions.—Identification errors are common in laboratory medicine, but most are detected before results are released, and only a fraction are associated with adverse patient events. Even when taking into consideration the design of this study, which used imperfect case finding, institutions that did a better job of detecting errors within the laboratory released a smaller proportion of results that involved specimen misidentification.
The Potential for Failure in Gynecologic Regulatory Proficiency Testing With Current Slide Validation Criteria: Results From the College of American Pathologists Interlaboratory Comparison in Gynecologic Cytology Program
Authors: Young Nancy A. , Moriarty Ann T. , Walsh Molly K. , Wang Edward , Wilbur David C.
Published: February 2021

Context.—Current regulatory proficiency testing scoring results in an automatic failure for identifying high-grade squamous intraepithelial lesion (HSIL) as negative.

Objective.—The College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology data from January 2004 to April 2005 were analyzed to estimate the percentage of failure based on negative responses for HSIL and validation criteria.

Design.—More than 15 000 participants received field-validated and educational slide sets for conventional, ThinPrep, and SurePath modules. Educational sets fulfilled the validation criteria of the Center for Medicare and Medicaid Services, which required the consensus diagnosis of biopsy-proven HSIL (not field-validated) after review by 3 pathologists. The College of American Pathologists field validation required at least 20 responses to the HSIL+ series, with 70% matched to HSIL+ (standard error ≤ 0.05). Minimum regulatory proficiency testing failure estimates were based on incorrect negative responses for the reference category of HSIL.

Results.—For both cytotechnologists and pathologists, there was a statistically significant higher failure rate for slides that were not field-validated versus those that were field-validated. In conventional modules, 5.3% of the slides that were not field-validated were called negative, versus 1.2% of the field-validated slides. In all liquid-based preparations, 4.0% of the non–field-validated versus 2.2% field-validated slides were called negative. Pathologists would have failed more often than cytotechnologists for the slides that were not field-validated, whereas there was no statistical difference in failure performance with field-validated slides.

Conclusions.—Failures were significantly greater with the slides that were not field-validated for both conventional and liquid-based preparations (ThinPrep only) and have implications for both regulatory proficiency testing and expert legal review. Poor performance of pathologists relative to that of cytotechnologists may reflect a lack of prescreening of slides or scope of practice issues.
Essential Thrombocythemia: A Review of Diagnostic and Pathologic Features
Authors: Sanchez Steven , Ewton April
Published: February 2021

Context.—Essential thrombocythemia (ET) is a chronic myeloproliferative disorder (CMPD) characterized predominately by thrombocytosis and abnormal megakaryocyte proliferation.

The current diagnostic criteria require a combination of clinical, histologic, and cytogenetic data. The diagnosis relies largely on exclusion of other causes of thrombocytosis.

Objective.—Describe historical, clinical, and laboratory features of ET in order to understand, clarify, and more accurately diagnose this entity.

Data Sources.—Review contemporary and historical literature on ET and other causes of thrombocytosis.

Conclusions.—ET is a relatively indolent and often asymptomatic CMPD that is characterized primarily by a sustained elevation in platelets ≥600 × 103/μL (≥600 × 109/L), proliferating enlarged and hyperlobated megakaryocytes, and minimal to absent bone marrow fibrosis. Significant changes and revisions to the diagnostic requirements and criteria for ET have occurred during the last 30 years. Recently, a mutation in the Janus kinase 2 (JAK2) gene has been found in a significant number of cases of ET and other CMPDs. In up to 57% of ET cases, a mutation in the JAK2 gene can be detected. In the absence of a JAK2 mutation and features of another CMPD, the diagnosis of ET remains a diagnosis of exclusion after other causes of thrombocytosis have been excluded.
Health Care Fraud and Abuse Laws
Authors: Klein Roger D. , Campbell Sheldon
Published: February 2021

Context.—Health care fraud and abuse enforcement actions have significantly expanded in number and scope during the past several years. The Department of Health and Human Services Office of Inspector General named review of in-office pathology services a critical priority in its 2005 Work Plan. As providers of pathology and laboratory medicine services, pathologists need to be aware of the potential impact of these laws on their practices.

Objectives.—To review the major statutes and regulations underlying most federal investigations and prosecutions of health care fraud, with a special emphasis on their relationships to pathology practice.

Design.—The authors reviewed pertinent federal statutes, regulations, and other documents, along with relevant legal literature.

Results.—The health care fraud and abuse laws are complicated and potentially impact pathology practice in unforeseen ways.

Conclusions.—The health care fraud and abuse laws are complex and often counterintuitive. The penalties for violation of these laws are severe. Because they may impact many areas of pathology and laboratory medicine practice, pathologists are advised to consult experienced legal counsel prior to embarking on potentially suspect health care arrangements.
Molecular Diagnosis of Sarcomas: Chromosomal Translocations in Sarcomas
Authors: Lazar Alexander , Abruzzo Lynne V. , Pollock Raphael E. , Lee Sangkyou , Czerniak Bogdan
Published: February 2021

Context.—Sarcomas are rare, numerous in type, and often difficult to definitively classify. Work in the last 2 decades has revealed that a significant subset of sarcomas are associated with specific chromosomal translocations producing chimeric (fusion) genes that play a role in the sarcomas' biology and are helpful in their differential diagnosis.

Objective.—To briefly review the sarcomas associated with specific translocations presenting Ewing sarcoma and synovial sarcoma as archetypes and to further explain how cytogenetic and molecular biologic approaches are being used in the diagnosis of sarcomas.

Data Sources.—This work is based on a selected review of the relevant medical and scientific literature and our extensive experience with molecular testing in sarcomas.

Conclusions.—In addition to, and complementing, the traditional diagnostic methods of examination of hematoxylin-eosin stained slides, immunohistochemistry, and sound clinical-pathologic correlation, additional cytogenetic and molecular biologic methods are being increasingly utilized and relied on in sarcoma pathology. These methods include chromosomal karyotyping, fluorescence in-situ hybridization, spectral karyotyping, and polymerase chain reaction– based methods for demonstrating specific chromosomal translocations and fusion genes. Understanding the basis of these methods and their application is critical to better provide accurate and validated specific diagnoses of sarcomas.
Mre11 Expression in Atypical Adenomatous Hyperplasia and Adenocarcinoma of the Lung
Authors: Nakanishi Kuniaki , Kumaki Fumiyuki , Hiroi Sadayuki , Mukai Makio , Ikeda Eiji , Kawai Toshiaki
Published: February 2021

Context.—The Mre11-Rad50-NBS1 complex plays an important role in telomere maintenance. Recently, it has been proposed that alterations in Mre11 function may be contributing factors in the development of some tumors. Moreover, mutations of Mre11 have been demonstrated to cause reduced Mre11 immunostaining.

Objective.—To investigate Mre11 in atypical adenomatous hyperplasia (AAH) and nonmucinous bronchioloalveolar carcinoma (NMBAC), an issue not previously explored.

Design.—We examined (1) the expression of Mre11 protein in 27 AAHs (9 lesions interpreted as low-grade AAH and 18 as high-grade AAH) and 40 NMBACs (using immunohistochemistry) and (2) Mre11 mRNA expression in 1 high-grade AAH and 6 NMBACs (using reverse transcription polymerase chain reaction). For the analysis of immunoreactivity, the intensity and extent of staining were each scored from 0 to 3. These 2 scores were summed to give in each case a final score of 0 to 6.

Results.—Scores for Mre11 expression were 5.0 ± 2.1 for low-grade AAH, 5.4 ± 1.2 for high-grade AAH, and 5.5 ± 0.9 for NMBAC, and there was no statistically significant difference among these 3 types of lesions. In the reverse transcription polymerase chain reaction for Mre11 mRNA, polymerase chain reaction products were detected in all samples.

Conclusions.—On this basis, we suggest that the part played by Mre11 in telomere maintenance may not be important for the progression of the adenoma–carcinoma (AAH–NMBAC) sequence in the lung, although some role for it in carcinogenesis cannot be completely ruled out.
Phyllodes Tumor: A Clinicopathologic and Immunohistochemical Study of 30 Cases
Authors: Esposito Nicole Nicosia , Mohan Deepak , Brufsky Adam , Lin Yan , Kapali Malathy , Dabbs David J.
Published: February 2021

Context.—Phyllodes tumors (PTs) of the breast are biphasic neoplasms composed of epithelium and a spindle-cell stroma. Currently, PTs are classified as benign, borderline, or malignant based on histopathologic features. However, histologic classification does not always predict outcome.

Objective.—To determine the prognostic value of a variety of clinicopathologic features and immunoreactivities in PTs.

Design.—Sixteen benign, 8 borderline, and 6 malignant PTs with follow-up were examined for reactivity across a panel of immunohistochemical stains, including c-Kit, endothelin 1, p16, p21, p53, and Ki-67. Clinicopathologic features, including stromal cellularity, mitotic rate, and margin status, were also assessed. Tumor variables were compared among tumor subgroups and between tumors that did and did not recur.

Results.—Of the 30 PTs, 4 recurred (1 benign, 2 borderline, 1 malignant). One patient with a malignant tumor died of metastatic disease 34 months after initial diagnosis. The overall positive rate of c-Kit immunoreactivity was 13% in benign, 63% in borderline, and 67% in malignant PTs. Endothelin 1 epithelial cytoplasmic staining was seen in 100% of benign, 50% of borderline, and 17% of malignant PTs. Additionally, p16, p21, p53, and Ki-67 were differentially expressed among benign, borderline, and malignant tumors. Positive surgical resection margins was the only variable that significantly predicted recurrent disease (P = .02).

Conclusions.—Stromal c-Kit positivity and epithelial endothelin 1 negativity are more often associated with malignant PTs; however, only positive margin status is significantly associated with tumor behavior.
Immunoreactivity of MIC2 (CD99) and Terminal Deoxynucleotidyl Transferase in Bone Marrow Clot and Core Specimens of Acute Myeloid Leukemias and Myelodysplastic Syndromes
Authors: Kang Loveleen C. , Dunphy Cherie H.
Published: February 2021

Context.—MIC2 (“thymus leukemia”) antigen has been shown to be expressed by T cells and monocytes, as well as B cells and granulocyte-lineage cells. It is most intensely expressed by the most immature thymus T-lineage cells and is more intensely expressed by CD34-positive/CD33-positive myeloid cells (compared to more mature myeloid cells) and the earliest CD34-positive/CD10-positive B-cell precursor cells (compared to cells of later B-cell precursor stages). CD99 (MIC2) is characteristically expressed in precursor B- and T-cell lymphoblastic lymphomas/leukemias, as well as in Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET). It has also been shown to be expressed in a few terminal deoxynucleotidyl transferase (TdT)–positive myeloid processes, but has been uniformly negative in TdT-negative myeloid processes. A more recent study showed that 43% of acute myeloid leukemias (AMLs) and 55% of chloromas express CD99, concluding that CD99 is commonly expressed in AML and rarely seen in myeloproliferative disorders, myelodysplastic syndromes, or normal bone marrow. Although this study speculated that MIC2 expression was probably not limited to TdT-positive AML, there was no comparison with TdT reactivity in this study.

Objective.—Since AML and high-grade myelodysplastic syndrome may occasionally be difficult to distinguish morphologically from acute lymphoblastic leukemia and ES/ PNET, we undertook a study to analyze MIC2 expression in conjunction with TdT reactivity in distinguishing AML or high-grade myelodysplastic syndrome from acute lymphoblastic leukemia and ES/PNET.

Design.—We studied bone marrow core and clot paraffin specimens from AML (classified according to criteria of the World Health Organization; n = 49), myelodysplastic syndromes (n = 4), precursor B-cell acute lymphoblastic leukemia (n = 4), ES/PNET (n = 1), and normal bone marrow (n = 3) with MIC2 (CD99) and TdT immunohistochemistry.

Results.—Overall, CD99 was expressed in 24 (49%) of 49 AML cases, including all (11/11) TdT-positive cases. CD99 was expressed in all subtypes of AML except M5. Myelodysplastic syndromes and normal bone marrow specimens were uniformly CD99 negative. Expression of TdT was limited to a subset of AML-M0, -M1, -M2, and -M4, and AML with multilineage dysplasia.

Conclusions.—In contrast to a previous study, CD99 expression was not restricted to TdT-positive hematologic proliferations. In particular, the CD99-positive M3 and M7 AMLs were TdT negative. An M5 AML may likely be excluded based on a uniform TdT-negative/CD99-negative immunophenotype. In addition, in our experience, CD99 should be routinely evaluated on bone marrow clots, owing to decreased reactivity or loss of reactivity in rapid decalcifying (RDO) solution–decalcified specimens.
Inflammatory Myofibroblastic Tumor of the Liver
Authors: Solomon Garron J. , Kinkhabwala Milan M. , Akhtar Mohammed
Published: February 2021

We report a case of hepatic inflammatory myofibroblastic tumor in a 26-year-old African American man who presented with right upper quadrant pain, weight loss, and fatigue during the previous year. Hepatomegaly was found on physical examination. Laboratory findings were significant for mild normocytic, normochromic anemia and elevated erythrocyte sedimentation rate. Imaging studies showed 2 contiguous masses suspicious for malignancy. A left partial hepatectomy was performed; the preoperative differential diagnosis was for angiosarcoma and hepatocellular carcinoma. The resected liver specimen showed 2 contiguous, firm, tan-white nodules that microscopically represented a proliferation of spindled myofibroblast cells set in an inflammatory and collagenized background. The spindle cells were strongly reactive for smooth muscle actin but negative for ALK-1. The morphologic and immunophenotypic findings, coupled with the clinical presentation, were consistent with an inflammatory myofibroblastic tumor of the liver.
Fatal Adenoviral Hepatitis After Rituximab Therapy
Authors: Iyer Anita , Mathur Radhika , Deepak Banglore V. , Sinard John
Published: February 2021

Rituximab is an anti-CD20 monoclonal antibody used in the treatment of B-cell proliferative disorders. Although it is very effective in many cases, a number of case reports in the literature have described fatal viral reactivations associated with rituximab therapy. We report what is to our knowledge the first case of fatal adenoviral hepatitis in a patient with Waldenstrom macroglobulinemia treated with rituximab. This case is a new example of an emerging pattern of association between rituximab therapy and fatal viral reactivations, and it urges increased vigilance when using rituximab-based treatment regimens.
Effect of Fondaparinux on Coagulation Assays: Results of College of American Pathologists Proficiency Testing
Authors: Smogorzewska Agata , Brandt John T. , Chandler Wayne L. , Cunningham Mark T. , Hayes Timothy E. , Olson John D. , Kottke-Marchant Kandice , Van Cott Elizabeth M.
Published: February 2021

Context.—Fondaparinux, a factor Xa inhibitor, is approved for thromboprophylaxis after orthopedic surgery and for treatment of venous thromboembolism. It may also be efficacious, safe, and cost-effective for other patients; thus, more widespread use of fondaparinux is likely. The effect of fondaparinux on coagulation testing needs to be thoroughly examined.

Objective.—To report the effects of fondaparinux on coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, factor VIII, thrombin time, anti–factor Xa) across diverse methodologies.

Design.—Samples with different concentrations of fondaparinux (0, 0.4, 0.8, and 2.0 μg/mL) were sent to laboratories participating in the College of American Pathologists Comprehensive Coagulation proficiency survey (N = 898). Laboratory-specific methods were used to assay coagulation parameters.

Results.—Prophylactic or therapeutic fondaparinux prolonged the prothrombin time by approximately 1 second and the activated partial thromboplastin time by 4 to 5 seconds, and reduced factor VIII from 119% to 107% and 102%, respectively. Supratherapeutic fondaparinux reduced factor VIII to 85%. The activated partial thromboplastin time was prolonged in 19%, 29%, and 52% of laboratories with prophylactic, therapeutic, and supratherapeutic fondaparinux levels, respectively. Fibrinogen, antithrombin, and thrombin time assays did not show clinically significant changes. When measuring fondaparinux concentration using an anti–factor Xa assay, the most accurate results were obtained when fondaparinux was used as the calibrator.

Conclusions.—Fondaparinux, even in prophylactic doses, slightly prolongs the prothrombin time and activated partial thromboplastin time and can interfere with factor VIII assays, but it has no clinically relevant effect on fibrinogen, antithrombin, or thrombin time. A fondaparinux standard curve should be used for reporting fondaparinux levels using an anti–factor Xa assay.
Specificity and Sensitivity of Hemosiderin-Laden Macrophages in Routine Bronchoalveolar Lavage in Children
Authors: Salih Zeynep N. , Akhter Afreen , Akhter Javeed
Published: February 2021

Context.—The presence of iron or hemosiderin in macrophages obtained in routine bronchoalveolar lavage is considered crucial in the diagnosis of the clinical syndrome of hemosiderosis. However, there do not appear to be any data on the sensitivity and specificity of the finding of hemosiderin-laden macrophages (HLMs) in bronchoalveolar lavage in children.

Objective.—To review data from bronchoalveolar lavage studies done in children to correlate the presence of HLMs with pneumonia and hemosiderosis and to determine what proportion of HLMs has the optimal sensitivity and specificity for the diagnosis of hemosiderosis.

Design.—One hundred ten bronchoalveolar lavage specimens obtained via flexible bronchoscopy were reviewed retrospectively. The data collected for demographics, indication for the bronchoscopy, diagnosis of pneumonia, anemia, and bronchoscopy and bronchoalveolar lavage findings were compared between patients diagnosed with hemosiderosis and those diagnosed with other diseases.

Results.—Six patients were diagnosed with hemosiderosis by clinical findings, lung biopsy, or autopsy. There were no statistical differences in pneumonia (P > .99), anemia (P > .99), or coughing (P = .08) between patients with hemosiderosis and other patients. Hemoptysis was the only symptom that was significantly different between the 2 groups (P = .04). The mean HLM index for patients with hemosiderosis was 56% ± 16.17% and for other patients, 7.5% ± 10.74% (P < .001). A HLM index of 35% gave a sensitivity of 1% and a specificity of .96%.

Conclusions.—These results confirm a strong association between HLM index and diagnosis of hemosiderosis in a pediatric population. Availability of this HLM index will result in accurate and timely diagnosis of pulmonary hemosiderosis, which may influence treatment and long-term prognosis.
Angioimmunoblastic T-Cell Lymphoma With Supervening Epstein-Barr Virus–Associated Large B-Cell Lymphoma
Authors: Hawley Robert C. , Cankovic Milena , Zarbo Richard J.
Published: February 2021

Patients with angioimmunoblastic T-cell lymphoma can have profound immune dysfunction and immunodeficiency. Epstein-Barr virus–driven B-cell lymphoid proliferation can occur in angioimmunoblastic T-cell lymphoma, as in other immunodeficiency states. However, few cases of Epstein-Barr virus–positive B-cell lymphoma arising in patients with preexisting angioimmunoblastic T-cell lymphoma have been reported. We report a case of angioimmunoblastic T-cell lymphoma in which diffuse large B-cell lymphoma developed 56 months after the diagnosis of angioimmunoblastic T-cell lymphoma. The patient survived for 9 years after the initial diagnosis of angioimmunoblastic T-cell lymphoma, and molecular studies performed on multiple biopsy specimens during this period revealed the dynamic nature of clonal lymphoid expansion. Epstein-Barr virus latent membrane protein 1 and Epstein-Barr virus– encoded RNA were detected in the diffuse large B-cell lymphoma, suggesting that Epstein-Barr virus may have played a role in the pathogenesis of the diffuse large B-cell lymphoma.
Large Natural Killer Cell Lymphoma Arising From an Indolent Natural Killer Cell Large Granular Lymphocyte Proliferation
Authors: Roullet Michele R. , Cornfield Dennis B.
Published: February 2021

Natural killer cell large granular lymphocyte proliferation is a relatively rare disorder that typically runs a chronic, indolent course. We present a patient with a 3½-year history of natural killer cell large granular lymphocyte proliferation terminating in large cell lymphoma with natural killer cell features. The diagnosis of natural killer cell large granular lymphocyte proliferation was based on flow cytometric demonstration of an expanded population of CD3− CD16+/CD56+ lymphocytes in the peripheral blood. The patient experienced various rheumatologic symptoms, but was hematologically stable for 3½ years. He then developed fevers, night sweats, weight loss, and a left lower lobe lung mass. Resection of the mass showed a large cell lymphoma with immunohistochemical positivity for CD2, CD7, CD56, and T-cell intracellular antigen-1, compatible with natural killer cell origin. In situ hybridization for Epstein-Barr virus and polymerase chain reaction analysis for T-cell receptor gene rearrangement were negative. To our knowledge, this is the second documented report of chronic natural killer cell large granular lymphocyte proliferation terminating in an aggressive large natural killer cell lymphoma.
Fine-Needle Aspiration Biopsy of Lymphoproliferative Disorders—Interpretations Based on Morphologic Criteria Alone: Results From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology
Authors: Young Nancy A. , Moriarty Ann T. , Haja Jennifer C. , Wilbur David C.
Published: February 2021

Context.—Diagnosis of lymphoproliferative disorders is one of the most challenging tasks faced by the cytologist. The initial cytomorphologic evaluation of lymphoproliferative lesions directs the choice of ancillary studies that ultimately lead to a diagnosis based on the World Health Organization classification system using a composite of clinical, morphologic, immunophenotypic, and molecular features.

Objective.—To evaluate the ability of participating laboratories in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology to appropriately categorize lymphoproliferative lesions based solely on cytomorphologic criteria.

Design.—Laboratory responses for lymph node aspirates were examined. All responses were based on review of glass slides without ancillary immunologic or molecular data available. The benchmarking data provided for each specific diagnosis were analyzed, with a focus on the performance for evaluation of lymphoproliferative lesions.

Results.—Based on morphology alone, responses for lymph node aspirates in the Non-Gynecologic Cytopathology program were correct to the exact reference diagnosis for 87.1% of Hodgkin lymphoma. Non-Hodgkin lymphoma was identified in 69.5% of the large cell non-Hodgkin lymphoma cases, of which 66.8% were correctly classified as large cell type. Non-Hodgkin lymphoma was identified in 68.1% of non-Hodgkin lymphoma, other than large cell cases, and of these, 94.7% were identified as other than large cell type.

Conclusions.—The spectrum of specific responses was consistent for lymphoproliferative lesions, with a reasonable differential diagnosis based on cytomorphology alone, which, in practice, facilitates the appropriate choice of immunophenotypic markers and other ancillary studies.
Causes of Death, Determined by Autopsy, in Previously Healthy (or Near-Healthy) Children Presenting to a Children's Hospital
Authors: Taggart Melissa W. , Craver Randall
Published: February 2021

Context.—Childhood mortality statistics are based on death certificates. The causes of death listed on death certificates may not be confirmed by autopsy findings, and mortality statistics may reflect deaths of many children with chronic disease. The diseases responsible for nontraumatic deaths of previously healthy children cannot be determined from these statistics.

Objective.—To identify causes of nontraumatic death in previously healthy or near-healthy children presenting to a children's hospital.

Design.—Retrospective review of autopsy protocols from 572 children who died at Children's Hospital of New Orleans in Louisiana between 1985 and 2003, with the premise that autopsy was done after most deaths of previously healthy or near-healthy children. Causes of death were grouped by disease processes and age groups and were compared to premortem clinical diagnoses.

Results.—Eighty-eight autopsy protocols were from children who were previously healthy or near healthy before the hospital admission during which they died. The median age was 11.4 months and the median length of stay was 2 days. Infection, primarily of the central nervous system and systemic (septicemia), was the most common cause of death (53%, 47 cases). Neoplasia, primarily of the central nervous and hematologic systems, was the second most common cause (15%, 13 cases). The predominant organ system involved with disease was the nervous system (36%, 32 cases). Unrecognized congenital disorders were found in approximately 10% of the cases.

Conclusions.—Infectious diseases are a frequent cause of death in previously healthy children. Fatal diseases most frequently affect the nervous system. Autopsy provides valuable information in the death of healthy children.
Histopathology of Gastric and Duodenal Strongyloides stercoralis Locations in Fifteen Immunocompromised Subjects
Authors: Rivasi Francesco , Pampiglione Silvio , Boldorini Renzo , Cardinale Loredana
Published: February 2021

Context.—Strongyloidiasis is a worldwide parasitic infection affecting approximately 75 million people. In Italy, it was more prevalent in the past among rural populations of irrigated areas.

Objective.—To determine the histopathologic alterations of the gastric and duodenal mucosa associated with the presence of Strongyloides stercoralis parasites.

Design.—Fifteen cases of strongyloidiasis were observed in immunocompromised patients during a recent 6-year period in Italy. S stercoralis was found histologically in gastric biopsies (10 cases), in a gastrectomy (1 case), and in duodenal biopsies (9 cases). In 5 cases the parasite was present both in gastric and duodenal biopsies. Four patients were affected by lymphoma, 2 by multiple myeloma, 2 by gastric carcinoma, 1 by chronic myeloid leukemia, 1 by sideroblastic anemia, 1 by colorectal adenocarcinoma, 1 by chronic idiopathic myelofibrosis, 1 by chronic gastritis, 1 by gastric ulcers, and 1 by rheumatoid arthritis in corticosteroid therapy. No patient was affected by human immunodeficiency virus infection. Strongyloidiasis was not clinically diagnosed.

Results.—Histologic examination revealed several sections of S stercoralis larvae, many eggs, and some adult forms. All the parasites were located in the gastric and/or the duodenal crypts. Eosinophils infiltrating into the lamina propria were found in all cases; their intensity was correlated with the intensity of the infection.

Conclusions.—Histologic diagnosis of strongyloidiasis must be taken into consideration when examining both gastric and duodenal biopsies in immunocompromised patients, to avoid the development of an overwhelming infection of the parasite, which is dangerous for the life of the patient.
A Synoptic Reporting System for Bone Marrow Aspiration and Core Biopsy Specimens
Authors: Murari Manjula , Pandey Rakesh
Published: February 2021

Context.—Advances in information technology have made electronic systems productive tools for pathology report generation. Structured data formats are recommended for better understanding of pathology reports by clinicians and for retrieval of pathology reports. Suitable formats need to be developed to include structured data elements for report generation in electronic systems.

Objective.—To conform to the requirement of protocol-based reporting and to provide uniform and standardized data entry and retrieval, we developed a synoptic reporting system for generation of bone marrow cytology and histology reports for incorporation into our hospital information system.

Design.—A combination of macro text, short preformatted templates of tabular data entry sheets, and canned files was developed using a text editor enabling protocol-based input. The system is flexible and has facility for appending free text entry. It also incorporates SNOMED coding and codes for teaching, research, and internal auditing.

Results.—This synoptic reporting system is easy to use and adaptable. Features and advantages include pick-up text with defined choices, flexibility for appending free text, facility for data entry for protocol-based reports for research use, standardized and uniform format of reporting, comparable follow-up reports, minimized typographical and transcription errors, and saving on reporting time, thus helping shorten the turnaround time.

Conclusions.—Simple structured pathology report templates are a powerful means for supporting uniformity in reporting as well as subsequent data viewing and extraction, particularly suitable to computerized reporting.
Pulse Granulomas Detected in Gallbladder, Fallopian Tube, and Skin
Authors: Rhee Dennis D. , Wu Mark Li-cheng
Published: February 2021

Context.—Foreign material typically elicits reactions dominated by multinucleated giant cells. Pulse granulomas are peculiar reactions to particles of food that are characterized by clusters of small to medium-sized hyaline rings. Pulse granulomas are rare and have occupied only the lungs, in association with aspiration, and the alimentary canal, in association with oral pathology, colonic diverticula, and a rectal mass.

Objective.—To report pulse granulomas that occupied previously unrecognized sites and to alert pathologists to the diagnostic pitfall of mistaking pulse granulomas for other entities.

Design.—We retrospectively reviewed 3 recently encountered cases that involved pulse granulomas in the gallbladder, fallopian tube, and skin.

Results.—In all cases, pulse granulomas were associated with fistulae involving the gastrointestinal tract. One fistula was clinically occult. Microscopy showed barium-laden histiocytes admixed with hyaline rings, with or without vegetable matter, confirming fistulae involving the gastrointestinal tract. Absence of other features of chronicity, including sarcoid-type granulomas and Langhans-type giant cells, helped to essentially exclude Crohn disease. In 1 case, hyaline rings of pulse granulomas closely resembled hyaline vasculopathy of amyloidosis, diabetes, or hypertension. Surprisingly, polariscopy failed to detect any vegetable matter. In 1 case, negative polariscopy contributed to the difficulty in finding rare vegetable matter.

Conclusions.—We demonstrated that pulse granulomas can occur outside the lungs and alimentary canal, and can be associated with fistulae involving the gastrointestinal tract. Awareness of this finding is necessary to avoid confusion with Crohn disease and hyaline vasculopathy. Polariscopy may fail to detect vegetable matter.
Extra-Axial Chordoma
Authors: DiFrancesco Lisa M. , Davanzo Castillo Cristobal A. , Temple Walley J.
Published: February 2021

Chordomas are low-grade malignant tumors of bone that occur almost exclusively in the axial skeleton. Other neoplasms with a similar histologic picture but an extra-axial location have been described, including parachordoma, myxoid chondrosarcoma, and extra-axial chordoma. We herein present another case of the rare extra-axial chordoma. A 41-year-old woman developed an 8.3 cm mass in the pubic bone. The gross, microscopic, and immunohistochemical findings were identical to those of a classic chordoma. Parachordoma and myxoid chondrosarcoma were excluded from the differential diagnosis. Five previously reported cases of extra-axial chordoma were reviewed and found also to demonstrate clinical and pathologic features specific to chordoma, despite arising in an extra-axial location. Although rare, extra-axial chordoma does exist and should be recognized and managed in a similar fashion to its well-described counterpart. It must be differentiated from other histologic mimics, because the treatment and prognosis can differ significantly.
Malignant Peripheral Nerve Sheath Tumor With Rhabdomyosarcomatous Differentiation (Malignant Triton Tumor)
Authors: Stasik Christopher J. , Tawfik Ossama
Published: February 2021

Malignant peripheral nerve sheath tumors arise from Schwann cells or within existing neurofibromas and have a strong association with type 1 neurofibromatosis. These tumors are histologically diverse and may contain malignant areas of divergent mesenchymal differentiation, the most common of which is skeletal muscle (rhabdomyosarcoma). Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation is also known as malignant triton tumor. Malignant triton tumor has a worse prognosis than classic malignant peripheral nerve sheath tumor does, and the correct diagnosis requires attention to the clinical history and knowledge of the complexities regarding its differential diagnosis. In this review we discuss the clinical, histopathological, immunohistochemical, and prognostic features of this rare neoplasm.
Primary Mucinous Adenocarcinoma of the Thymus: A Case Report and Review of the Literature
Authors: Kapur Payal , Rakheja Dinesh , Bastasch Michael , Molberg Kyle H. , Sarode Venetia R.
Published: February 2021

Primary thymic mucinous adenocarcinoma is extremely rare; to our knowledge, only 2 cases have been reported to date. We describe a third case of primary mucinous adenocarcinoma of the thymus in a 41-year-old man who presented with an anterior mediastinal mass with subsequent metastasis to the lung. The initial diagnosis was of metastatic mucinous adenocarcinoma, but extensive clinical workup of the patient failed to reveal a primary tumor elsewhere in the body. The specific identification of mucinous adenocarcinoma as a primary thymic neoplasm can be difficult or impossible. Morphologic and immunophenotypic similarities to mucinous adenocarcinomas of the gastrointestinal tract can pose diagnostic challenges for surgical pathologists, especially in small biopsy specimens.
Multiorgan Involvement in Nephrogenic Fibrosing Dermopathy: An Autopsy Case and Review of the Literature
Authors: Gibson Sarah E. , Farver Carol F. , Prayson Richard A.
Published: February 2021

Nephrogenic fibrosing dermopathy is a recently recognized, scleromyxedema-like fibrosing skin condition that occurs in individuals with acute or chronic renal failure. Although the early descriptions of this disorder describe a purely cutaneous disease process, 2 recent autopsy reports have identified apparent multiorgan fibrosis with involvement of skeletal muscle, myocardium, lungs, kidneys, and testes. We describe a 23-year-old man with nephrogenic fibrosing dermopathy and significant fibrosis of the atrial myocardium and dura mater, which was identified at autopsy. Dural fibrosis is a previously undescribed systemic manifestation of nephrogenic fibrosing dermopathy. The literature is reviewed.