bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular Proliferative Fraction Measured With Topoisomerase IIα Predicts Malignancy in Endocrine Pancreatic Tumors
Authors: Diaz-Rubio Jose Luis , Duarte-Rojo Andres , Saqui-Salces Milena , Gamboa-Dominguez Armando , Robles-Diaz Guillermo
Published: February 2021

Context.—Endocrine pancreatic tumors (EPTs) are rare lesions with varying biological behavior. Establishing malignancy is a challenge for clinicians and pathologists.

Objective.—To establish the role of proliferative, apoptotic, angiogenic, and hormonal markers as predictors of malignancy in EPTs.

Design.—Paraffin-embedded EPT samples were studied for prognostic markers.

Patients.—Twenty-one consecutive patients with a diagnosis of EPT.

Main Outcome Measures.—The proliferative fraction (topoisomerase IIα), microvascular density (CD34), vascular endothelial growth factor expression, and estrogen receptor-beta (ERβ) expression were studied by immunohistochemistry on all EPTs. Apoptosis was also assessed with terminal deoxynucleotidyl transferase nick-end labeling.

Results.—We identified 13 benign and 8 malignant tumors. Topoisomerase IIα was significantly increased in malignant tumors (P = .001), while there were no differences in apoptosis, microvascular density, or vascular endothelial growth factor expression in association with malignancy. No correlation could be identified between microvascular density and vascular endothelial growth factor expression, and ERβ was not detected. A receiver operating characteristic curve for topoisomerase IIα disclosed that above a labeling index of 13, the test had 88% sensitivity and 100% specificity for predicting malignancy.

Conclusion.—Cellular proliferation measured with topoisomerase IIα is a simple prognostic marker for malignancy in EPTs, unlike apoptosis, angiogenesis, or the presence of ERβ, which were not associated with malignant behavior. These findings designate a defined field for future research on endocrine pancreatic carcinogenesis and a possible target for chemotherapeutic agents.
The Spectrum of Kit (CD117) Immunoreactivity in Lung and Pleural Tumors: A Study of 96 Cases Using a Single-Source Antibody With a Review of the Literature
Authors: Butnor Kelly J. , Burchette James L. , Sporn Thomas A. , Hammar Samuel P. , Roggli Victor L.
Published: February 2021

Context.—The development of successful chemotherapeutic agents directed against the Kit receptor tyrosine kinase protein has generated intense interest in the Kit (CD117) immunoreactivity of various neoplasms. Immunoreactivity for Kit in small cell lung carcinoma (SCLC) has been well established. However, data on Kit immunostaining in other lung tumors is limited. Likewise, while solitary fibrous tumors of the gastrointestinal tract have been examined for Kit expression, the Kit staining characteristics of their counterpart in the pleura, namely, localized fibrous tumor, are not well known.

Objective.—To characterize the Kit immunohistochemical profiles of major types of lung and pleural tumors.

Design.—We stained 60 lung carcinomas, including 11 SCLCs, 4 large cell neuroendocrine carcinomas, 22 squamous cell carcinomas, 23 adenocarcinomas, 11 pulmonary carcinoid tumors, 19 pleural malignant mesotheliomas, and 6 localized pleural fibrous tumors with a commonly used polyclonal Kit antibody.

Results.—Small cell lung carcinomas demonstrated Kit staining in 82% of cases, nearly all of which demonstrated moderate to intense immunoreactivity. Immunostaining was observed in 25% of large cell neuroendocrine carcinomas. Focal staining was observed in 9% of squamous cell carcinomas and 17% of adenocarcinomas. None of the pulmonary carcinoid tumors were immunoreactive. Moderately intense immunostaining was present in 50% of localized fibrous tumors. Malignant mesotheliomas were nonimmunoreactive for Kit in 95% of cases.

Conclusion.—Non–small cell lung carcinomas showed very limited expression of Kit. Lung tumors with neuroendocrine differentiation exhibited a wide spectrum of Kit immunoreactivity, ranging from rare in pulmonary carcinoid tumors to frequent in SCLC. The high frequency of Kit immunostaining in SCLC has important potential therapeutic implications. Demonstration of Kit positivity in some localized fibrous tumors in this study contrasts with absent immunoreactivity in solitary fibrous tumors of the gastrointestinal tract. The paucity of Kit staining in malignant mesothelioma suggests these tumors are unlikely to respond to currently available tyrosine kinase inhibitors.
Calibration Verification Performance Relates to Proficiency Testing Performance
Authors: Kroll Martin H. , Styer Patricia E. , Vasquez Delmiro Anthony
Published: February 2021

Context.—Since 1988, the College of American Pathologists has been offering materials for calibration verification coupled with the surveys for linearity, called the linearity (LN) surveys.

Objective.—To determine whether successful completion of the College of American Pathologists LN surveys provides a benefit in terms of improved proficiency testing (PT) performance.

Design.—In this study, we used information from LN surveys LN1/2, LN3, and LN5 and from the PT surveys C, Z, and K administered and analyzed in the year 2000. For the PT data, we calculated 4 measures of performance: passing PT, results exceeding 2 SDs, sum of absolute SD intervals, and the absolute sum of SD intervals. For the LN data, we classified laboratories as participants versus nonparticipants in LN surveys and by whether or not LN survey performance was successful.

Results.—LN enrollees had fewer unacceptable PT results than did nonenrollees. Additionally, for many analytes there was a significant positive association between LN performance and PT performance.

Conclusions.—For most analytes studied, there was strong evidence linking performance on PT surveys with performance on LN surveys. Eight of 13 analyses (62%) demonstrated improved performance with successful calibration verification.
Carcinoid Tumor Arising in a Tailgut Cyst of the Anorectal Junction With Distant Metastasis: A Case Report and Review of the Literature
Authors: Song Dong Eun , Park Jean Kyung , Hur Bang , Ro Jae Y.
Published: February 2021

Tailgut cyst is a rare congenital presacral lesion and is believed to arise from the persistent remnants of the postanal gut. Malignancy occurring in a tailgut cyst is extremely rare, and to our knowledge only 5 cases of carcinoid tumor arising in a tailgut cyst have been reported in the literature to date. We report a sixth case of carcinoid tumor arising in a tailgut cyst. The patient was a 41-year-old woman who presented with perianal pain. Sigmoidoscopy showed a 2-cm submucosal mass located 4 cm above the anal verge. The mass was a multilocular cyst with gray-tan solid portions. The cyst was lined by ciliated columnar, squamous, and transitional epithelia with small foci of carcinoid tumor in the cystic wall. The carcinoid tumor showed a trabecular growth pattern with uniform oval or round cells containing fine chromatin and positive immunoreactivity for chromogranin, synaptophysin, and cytokeratin. This case was unique because the tumor occurred at the anorectal junction, not in the retrorectal space, and unlike previously reported cases showed aggressive behavior and distant metastases.
Management Training for Pathology Residents
Authors: Horowitz Richard E. , Naritoku Wesley , Wagar Elizabeth A.
Published: February 2021

Context.—Success in the practice of pathology demands proficiency in management, but management training for pathology residents is generally inadequate, with little agreement on an appropriate curriculum or competency assessment. Most residency training programs do not have faculty members who are interested and have expertise in management and who are dedicated to and have time available for teaching.

Objective.—To develop a didactic management training program for the residents from 6 separate pathology residency programs in Southern California, with a comprehensive curriculum taught by experts in each area without undue burden on any single training program.

Methods.—Faculty from the University of California–Los Angeles and the University of Southern California reviewed the literature and the management needs of practicing pathologists and devised the curriculum. Pathologist and nonpathologist speakers were identified who were working in important management positions both regionally and nationally. Seminars were presented in alternate months during a 2-year period. Sessions were videotaped, and each session was evaluated by the attendees.

Results.—The curriculum consisted of 12 major topics, and seminars were delivered by 15 presenters from 6 institutions. Attendance was highest for residents in postgraduate years 2 and 3. The overall evaluation scores were exceedingly high (4.66 of a possible 5.0), and residents reported a significant increase in subject knowledge. Videotaping of presentations provided flexibility for residents who were unable to attend the seminars.

Conclusion.—This program was effective and could serve as a template for other pathology residency training programs to establish curriculum content and develop resident competency. Teaching responsibilities were less burdensome when spread among several programs and when supplemented by nonpathology faculty. Electronic and audiovisual support enhanced flexibility and access to the program.
Kaposiform Hemangioendothelioma Associated With Nonimmune Fetal Hydrops
Authors: Martinez Antonio E. , Robinson Morton J. , Alexis John B.
Published: February 2021

We describe the case of a 31-week fetus who died in utero with an invasive retroperitoneal kaposiform hemangioendothelioma. This rare vascular neoplasm usually presents as a localized violaceous skin lesion in infants and behaves in a benign fashion; however, kaposiform hemangioendothelioma may present as an invasive neoplasm of the chest or abdominal cavity, where it can lead to the Kasabach-Merritt syndrome, which consists of thrombocytopenia, consumptive coagulopathy, and microangiopathic anemia in association with a vascular anomaly. The case we describe is unique in that the tumor presented in utero and led to intrauterine nonimmune fetal hydrops. Kaposiform hemangioendothelioma has been described in utero; however, to our knowledge, intrauterine fetal death as a direct consequence has not been reported previously in the literature.
Overexpression of Human Carcinoma–Associated Antigen in Urothelial Carcinoma of the Bladder
Authors: Yao Jorge L. , Bourne Patricia A. , Yang Qi , Lei Junyi , di Sant'Agnese P. Anthony , Huang Jiaoti
Published: February 2021

Context.—Human carcinoma–associated antigen (HCA) is a mucin protein whose level is increased in the sera of patients with a variety of carcinomas. We have previously shown that prostatic carcinoma overexpresses HCA in comparison to benign prostatic tissue. To our knowledge, expression of HCA in other tumors has not been reported previously.

Objective.—The current study was designed to determine if HCA is overexpressed in urothelial carcinoma (UCa) of the bladder.

Design.—Forty cystectomy specimens with UCa were selected, of which 27 cases had invasive UCa, 21 cases had a noninvasive component, and 36 cases had benign urothelium. Seven cystectomy specimens with benign conditions were chosen as controls. Anti-HCA monoclonal antibody HAE3 was used for immunohistochemical staining. Results were recorded as positive (≥5% of cells staining and staining intensity 2+ or 3+) or negative (<5% of cells staining or staining intensity <2+) and analyzed using the Fisher exact test.

Results.—HAE3 staining was positive in 67% of invasive UCa, 29% of noninvasive UCa, but only 5% of benign urothelium specimens. The difference in HCA expression between benign urothelium and UCa and that between invasive and noninvasive UCa was statistically significant (P = .008). No statistically significant difference was found between low-grade and high-grade noninvasive papillary UCa (P = .06).

Conclusions.—Human carcinoma–associated antigen is selectively overexpressed in a significant number of cases of UCa of the bladder, suggesting the potential utility of monitoring the serum and/or urine levels of HCA in monitoring patients with HCA-positive UCa for recurrence or progression.
Fibrous Dysplasia With Degenerative Atypia: A Benign Lesion Potentially Mistaken for Sarcoma
Authors: Bertoni Franco , Fernando Arias Luis , Alberghini Marco , Bacchini Patrizia
Published: February 2021

Fibrous dysplasia is a benign disorder of bone in which proliferating fibrous tissue replaces the bony spongiosa. Cytologic atypia is generally not considered a feature of this proliferating tissue. We present a case of fibrous dysplasia with marked atypical nuclear changes consistent with degenerative or regressive changes. A 42-year-old man presented with an osteolytic lesion of the right iliac bone. Histologic study demonstrated a fibro-osseous lesion with woven bone trabeculae and bland-looking fibrous tissue. Several areas showed atypical cells with enlarged pleomorphic nuclei and bizarre features. There was no change in the nuclear-cytoplasmic ratio nor were mitotic figures identified. The differential diagnosis is discussed. When radiographic and other histologic findings suggest fibrous dysplasia, the atypical nuclear changes should not, by themselves, alter the diagnosis.
Extramammary Paget Disease of the Scrotum With Features of Bowen Disease
Authors: Quinn Adam M. , Sienko Anna , Basrawala Zane , Campbell Steve C.
Published: February 2021

The scrotum is an uncommon site for the presentation of extramammary Paget disease (EMPD). We describe a case of EMPD that was discovered in a patient who had been previously diagnosed and treated for squamous cell carcinoma in situ of the scrotum 3 years earlier. Pathologic examination of the current scrotectomy specimen revealed an erythematous patch with areas of pale induration. Microscopic examination revealed areas with the characteristic histology of Paget disease adjacent to areas characteristic of Bowen disease. Immunohistochemical findings demonstrated a strong expression of carcinoembryonic antigen, cytokeratin 7, and low-molecular-weight cytokeratins (CAM 5.2) in both of these areas, giving support to the overall diagnosis of EMPD. High-molecular-weight cytokeratins (34βE12) were uncharacteristically expressed in the cytoplasm of the Paget cells with equal or greater strength than in the surrounding keratinocytes, suggesting some degree of squamous differentiation. Very few publications have reported the coexistence of EMPD with squamous cell carcinoma in situ, occurring mostly in the vulva. To our knowledge, our case is the first report of scrotal EMPD with features of Bowen disease. Our findings support the theory that primary EMPD arises multifocally from multipotential epidermal cells.
Eosinophilic Angiocentric Fibrosis
Authors: Önder Sevgen , Sungur Arzu
Published: February 2021

We present the case of a 45-year-old man who presented with medication-resistant chronic bilateral nasal obstruction. The patient had no known history of allergy or any other disease. Nasal septoplasty was performed to relieve his symptoms. Histologically, thick collagen bundles were seen, characteristically whorling around vessels in a fibrotic stroma. Inflammatory cells, rich in eosinophils, were scattered throughout the lesion. No granulomas, necrosis, or vessel destruction were present. A diagnosis of eosinophilic angiocentric fibrosis was made. This neoplasm, which has very characteristic histologic features, is a rare entity of the sinonasal tract.
Russell Body Gastritis: An Unusual, Tumor-like Lesion of the Gastric Mucosa
Authors: Erbersdobler Andreas , Petri Susan , Lock Guntram
Published: February 2021

The case of an 80-year-old woman who presented with epigastric symptoms is reported. Upper gastrointestinal endoscopy displayed Candida esophagitis and a localized swelling of the fundic mucosa. Histologic examination of the gastric biopsy showed a distinctive accumulation of numerous uniform plasma cells filled with so-called Russell bodies. On low-power view, the lesion resembled a neoplastic process due to the marked expansion of the lamina propria with distension of fundic glands. However, immunohistochemistry confirmed a polyclonal pattern of the plasma cells. This unusual reactive lesion of the gastric mucosa has only rarely been described and has been termed Russell body gastritis.
Chondroid Syringoma
Authors: Salama Mohamed E. , Azam Muhammad , Ma Chan K. , Ormsby Adrian , Zarbo Richard J. , Amin Mahul B. , Lee Min W.
Published: February 2021

Context.—Chondroid syringoma (CS) is a benign cutaneous adnexal tumor with epithelial and stromal components. Epithelial components derived from folliculo-sebaceous-apocrine germ are evident in apocrine but not in eccrine CS.

Objectives.—To further characterize pilosebaceous differentiation and to identify the presence of Merkel cells in the areas of follicular differentiation.

Design.—Histologic type, folliculo-sebaceous differentiation, character of stroma, and presence or absence of Merkel cells by cytokeratin (CK) 20 immunoreactivity were evaluated in 25 CSs (22 apocrine and 3 eccrine) from the surgical pathology files of Henry Ford Hospital (Detroit, Mich).

Results.—Most CSs occurred in the head and neck region of patients aged 40 years or older. We found no significant difference in sex, age, or location between apocrine and eccrine types. The stroma varied from myxoid (100%) to chondroid (59%), with various amounts of fat (59%) and ossification identified in 2 cases (9%) of apocrine type, but was homogeneously myxoid in the eccrine type. Follicular and sebaceous differentiation was found in 64% and 32% of apocrine CSs, respectively. Only 2 (14%) apocrine CSs with follicular differentiation were positive for CK20 (a few scattered cells in one case and numerous grouped cells in the other in association with follicular epithelium). No correlation was found between type of stroma and the presence of Merkel cells. Scattered Merkel cells were identified in 83% of normal hair follicles and in 33.3% of normal epidermis.

Conclusion.—A high proportion of apocrine CSs show folliculo-sebaceous differentiation. The presence of Merkel cells in foci of follicular differentiation of CS supports the hypothesis that Merkel cells may be an integral constituent of follicles. To our knowledge, the presence of Merkel cells in CS, particularly in proliferative form, has not been described previously in the literature.
Febrile Nonhemolytic Transfusion Reactions
Authors: Ezidiegwu Christian N. , Lauenstein Karla J. , Rosales Lazaro G. , Kelly Karen C. , Bernard Henry John
Published: February 2021

Context.—Febrile nonhemolytic transfusion reactions (FNHTRs) cause unwelcome interruptions during the course of blood product transfusions and necessitate measures to verify the nature of the reaction and to exclude certain dangerous reactions, such as hemolytic and septic phenomena.

Objective.—To examine transfusion medicine data to determine the clinical implications of the routine administration of antipyretic medication to adult patients before transfusion for the prevention of FNHTRs.

Design.—A retrospective review was conducted of FNHTR data during 5 years (1998–2002), and a determination was made of the cost of a transfusion complicated by an FNHTR. In addition, a comparative cost analysis was performed using our data and published data on the incidence of FNHTRs. The clinical implications of medication with respect to possible drug-induced adverse effects were assessed, as well as the potential interference with diagnosing other forms of transfusion reactions and the mitigation of the clinical effect of an FNHTR.

Results.—For nearly 120 000 U of transfused blood components, approximately 80% of which were preceded by antipyretic medication during the study period, the overall incidence of FNHTR was found to be 0.09%. Furthermore, there was no evidence of antipyretic-associated complications, nor any evidence that antipyretics prevented the recognition of other more dangerous complications of transfusions.

Conclusion.—Our findings indicate that this practice provides significant advantages to the recipient of a transfusion, but does not appear to yield significant cost benefits for the health care provider.
47,XXY With Associated Bilateral Renal Agenesis
Authors: Barroeta Julieta E. , Stopyra Gary A.
Published: February 2021

We describe the case of a 36-week gestational-age male stillborn with bilateral renal agenesis and a 47,XXY karyotype, as well as features of Potter sequence. No other congenital abnormalities were noted. Severe oligohydramnios was diagnosed prenatally at 30 weeks, and cytogenetic analysis was performed postmortem. Urinary tract anomalies are uncommon in association with Klinefelter syndrome. Unilateral renal agenesis has been described. We describe, to our knowledge, the first case of bilateral renal agenesis in association with 47,XXY.
Fine-Needle Aspirates of Adenocarcinoma/Metastatic Carcinoma That Resemble Hepatocellular Carcinoma: Correlating Cytologic Features and Performance in the College of American Pathologists Nongynecologic Cytology Program
Authors: Renshaw Andrew A. , Haja Jennifer , Wilbur David C. , Miller Theodore R.
Published: February 2021

Context.—The cytologic features of adenocarcinoma/ metastatic carcinoma in liver fine-needle aspirates are well described. We review the cytologic findings from 16 aspirates of adenocarcinoma/metastatic carcinoma that were frequently misclassified as hepatocellular carcinomas and compare them with 17 cases that were rarely misclassified.

Objective.—To compare the cytologic features of adenocarcinoma/metastatic carcinoma in fine-needle aspiration specimens of the liver that were frequently misclassified as hepatocellular carcinoma with those of aspirates that were rarely misclassified.

Design.—We reviewed a total of 1712 interpretations from 33 different cases of adenocarcinoma/metastatic carcinoma tumor in liver fine-needle aspiration specimens in the College of American Pathologists Nongynecologic Cytology Program and correlated the cytologic features with performance in the program.

Results.—Overall, cases that were frequently misclassified as hepatocellular carcinoma were misclassified on average 26% of the time (range, 13%–54%), while infrequently misclassified cases were interpreted as hepatocellular carcinoma on average 0.7% of the time (range, 0%– 3%). The difference was statistically significant (P < .001). On review, cases that were frequently misclassified most often had moderate amounts of granular cytoplasm (16/16 cases) and round nuclei with even chromatin (13/16 cases). Trabeculae (3/16 cases), bare nuclei (2/16 cases), and endothelial wrapping (1/16 cases) were also occasionally present. In contrast, cases that were rarely misclassified were more likely to have areas with cells showing scant cytoplasm that were crowded and overlapped or molded (13/17 cases) and contained dark hyperchromatic chromatin (13/17 cases) compared to cases that were frequently misclassified (P < .001 and P = .002, respectively). Trabeculae (2/17) and bare nuclei (2/17 cases) were also rarely present.

Conclusion.—Cases of adenocarcinoma/metastatic carcinoma with moderate amounts of granular cytoplasm and round nuclei with even chromatin are frequently misclassified as hepatocellular carcinoma. Recognition of this problem, attention to cytologic criteria, and frequent use of immunohistochemical studies and core biopsy may help avoid this pitfall.
Error Detection in Anatomic Pathology
Authors: Zarbo Richard J. , Meier Frederick A. , Raab Stephen S.
Published: February 2021

Objectives.—To define the magnitude of error occurring in anatomic pathology, to propose a scheme to classify such errors so their influence on clinical outcomes can be evaluated, and to identify quality assurance procedures able to reduce the frequency of errors.

Design.—(a) Peer-reviewed literature search via PubMed for studies from single institutions and multi-institutional College of American Pathologists Q-Probes studies of anatomic pathology error detection and prevention practices; (b) structured evaluation of defects in surgical pathology reports uncovered in the Department of Pathology and Laboratory Medicine of the Henry Ford Health System in 2001–2003, using a newly validated error taxonomy scheme; and (c) comparative review of anatomic pathology quality assurance procedures proposed to reduce error.

Results.—Marked differences in both definitions of error and pathology practice make comparison of error detection and prevention procedures among publications from individual institutions impossible. Q-Probes studies further suggest that observer redundancy reduces diagnostic variation and interpretive error, which ranges from 1.2 to 50 errors per 1000 cases; however, it is unclear which forms of such redundancy are the most efficient in uncovering diagnostic error. The proposed error taxonomy tested has shown a very good interobserver agreement of 91.4% (κ = 0.8780; 95% confidence limit, 0.8416–0.9144), when applied to amended reports, and suggests a distribution of errors among identification, specimen, interpretation, and reporting variables.

Conclusions.—Presently, there are no standardized tools for defining error in anatomic pathology, so it cannot be reliably measured nor can its clinical impact be assessed. The authors propose a standardized error classification that would permit measurement of error frequencies, clinical impact of errors, and the effect of error reduction and prevention efforts. In particular, the value of double-reading, case conferences, and consultations (the traditional triad of error control in anatomic pathology) awaits objective assessment.
Graft Vascular Disease After Cardiac Transplantation and Its Relationship to Mean Acute Rejection Score
Authors: Alexander Russell T. , Lathrop Sarah , Vollmer Robin , Blue Laura , Russell Stuart D. , Steenbergen Charles
Published: February 2021

Context.—Graft vascular disease remains a significant source of morbidity and mortality in heart transplant patients. The influence of acute cellular rejection on the development of graft vascular disease is controversial.

Objective.—To determine the relationship between mean acute cellular rejection score and the presence of atherosclerosis or fibrointimal hyperplasia in cardiac allografts at autopsy.

Design.—This retrospective, autopsy-based study examined 27 heart transplant patients to evaluate for graft vascular disease. A rejection score for each patient was calculated as the average of all the rejection scores determined by endomyocardial biopsy. Gross and histologic examination of the heart was used to divide patients into 3 groups: no coronary artery disease, atherosclerosis, and fibrointimal hyperplasia. Mean rejection scores were calculated for each of these groups for all patients and patients who survived longer than 3 months. Mean rejection scores were compared by an analysis of variance and pairwise t tests.

Results.—Mean rejection scores demonstrated a trend of increasing value from no coronary disease (0.323) to atherosclerosis (0.569) to fibrointimal hyperplasia (0.835). Only fibrointimal hyperplasia had a significantly higher mean rejection score compared with patients with no coronary disease when examined in all patients (P = .01) and in patients who survived longer than 3 months (P = .049).

Conclusion.—This study showed that the development of coronary artery fibrointimal hyperplasia, but not atherosclerosis, was significantly related to mean acute rejection score.
Passive Seeding in Metanephric Adenoma: A Review of Pseudometastatic Lesions in Perinephric Lymph Nodes
Authors: Paner Gladell P. , Turk Thomas M. , Clark Joseph I. , Lindgren Valerie , Picken Maria M.
Published: February 2021

Lymph node involvement derived from a discrete neoplastic process fundamentally implies tumor malignancy. However, rarely, inconsequential passive transport of benign neoplastic cells to the lymph node can occur and may cause confusion as to the nature of the neoplasm (ie, malignant vs benign). We describe a 10-cm right renal metanephric adenoma incidentally discovered in a 30-year-old woman during cesarean section for a triplet pregnancy. Subsequent nephrectomy following an equivocal needle biopsy diagnosis showed histologic features classic for metanephric adenoma, including the lack of cytologic atypia and mitoses. Necrosis present in this lesion appeared to be secondary to tumor physical disruption. The tumor cells were positive for Wilms tumor 1 (WT1) antigen, pankeratin, and CD57, focally positive for epithelial membrane antigen, and negative for cytokeratin 7, cytokeratin 34βE12, and CD56. Electron microscopy confirmed the tumor's epithelial nature, and cytogenetics revealed a diploid 46XX karyotype. The tumor proliferation index with Ki-67 was only 3% to 5% and the proliferating cell nuclear antigen index was 0%. A single, concurrently resected hilar lymph node contained scattered subcapsular, sinusoidal, and focally intralymphovascular psammoma bodies along with occasional adherent epithelial cells. These cells were highlighted by pankeratin but were nonreactive to WT1 antigen, similar to the nonviable cells in the primary tumor. Clinical surveillance and follow-up showed no disease recurrence 4 years after nephrectomy. We postulate that the lymph node inclusions found in this case represent passive transport of neoplastic cells to the lymph node following manipulation of the renal mass. We conclude that this phenomenon is understudied and underrecognized and can easily be mistaken for metastasis.
Inflammatory Sarcomatoid Carcinoma: A Case Report and Discussion of a Malignant Tumor With Benign Appearance
Authors: Antic Tatjana , Kapur Umesh , Vigneswaran Wickii T. , Oshima Kiyoko
Published: February 2021

Inflammatory sarcomatoid carcinoma is an aggressive tumor with an unusually benign appearance. We report the case of a 65-year-old man with a history of inoperable poorly differentiated carcinoma of the right lung, for which he had received chemoradiotherapy. A new solitary mass was discovered 4 years later in the left lung on surveillance computed tomography. The patient underwent thoracotomy with a wedge biopsy on which frozen section was performed. The nodule was vaguely granulomatous and associated with a mixed inflammatory infiltrate and a deceptively bland spindle cell proliferation. Results of immunoperoxidase studies, however, showed that the nodule contained neoplastic cells with an epithelial phenotype that were invading the pulmonary vessels. These are features of the rare inflammatory sarcomatoid carcinoma. In contrast to sarcomatoid carcinomas, this case highlights the deceptively benign appearance of inflammatory sarcomatoid carcinoma. This leads us to concur with the recommendation to exercise caution when attempting the diagnosis of apparently benign lesions on intraoperative frozen section in patients with high clinical suspicion of malignancy.
What's New in Hereditary Colorectal Cancer?
Authors: Jass Jeremy R.
Published: February 2021

Precancerous polyposes other than classic familial adenomatous polyposis and the condition hereditary nonpolyposis colorectal cancer, or Lynch syndrome, continue to present major diagnostic challenges for the anatomic pathologist. This editorial highlights the practical significance of novel insights and clinical guidelines in the recent literature, as well as in 4 contributions to this edition of the Archives of Pathology & Laboratory Medicine. The first section will address attenuated familial adenomatous polyposis and a newly recognized type of autosomal-recessive adenomatous polyposis associated with the DNA repair gene MYH. The remainder of the editorial discusses the role of the revised Bethesda guidelines in the diagnosis of hereditary nonpolyposis colorectal cancer and concludes with the recently identified serrated pathway syndrome.
High-Grade Pancreatic Intraepithelial Neoplasia in a Patient With Familial Adenomatous Polyposis
Authors: Gupta Chakshu , Mazzara Paul F.
Published: February 2021

Familial adenomatous polyposis (FAP) is caused by mutation of the adenomatous polyposis coli (APC) gene and is characterized by multiple colorectal adenomas and tumors of other organs and sites. A 58-year-old woman with FAP syndrome and previous total colectomy presented for routine follow-up examination. Abdominal ultrasound and subsequent endoscopic evaluation revealed ampullary and duodenal polyps, as well as inhomogeneity of the pancreatic head. A pancreaticoduodenectomy confirmed multiple duodenal adenomas. In addition, high-grade pancreatic intraepithelial neoplasia (PanIN-3) was found in the smaller pancreatic ducts. Pancreatic precancerous lesions have only rarely been described in FAP, including 2 pancreatic duct adenomas and 2 intraductal papillary mucinous neoplasms. A review of the world English literature revealed no reports of PanIN-3 in association with FAP. Further studies are required to determine if patients with FAP are at increased risk for pancreatic premalignant lesions.
Differential Diagnosis of Benign and Malignant Mesothelial Proliferations on Pleural Biopsies
Authors: Cagle Philip T. , Churg Andrew
Published: February 2021

Context.—Although much of the pathology literature focuses on differential diagnosis of diffuse malignant mesothelioma from other types of cancer, the primary diagnostic challenge facing the pathologist is often whether a mesothelial proliferation on a pleural biopsy represents a malignancy or a benign reactive hyperplasia.

Design.—Based on previous medical publications, extensive personal consultations, and experience on the United States–Canadian Mesothelioma Reference Panel and the International Mesothelioma Panel, salient information was determined about interpretation of benign versus malignant mesothelial proliferations on pleural biopsies.

Results.—Differentiation of benign reactive mesothelial hyperplasia from diffuse malignant mesothelioma is often difficult. Benign reactive mesothelial hyperplasia may mimic many features ordinarily associated with malignancy, and diffuse malignant mesothelioma may be cytologically bland. Entrapment of benign reactive mesothelial cells within organizing pleuritis may mimic tissue invasion.

Conclusions.—Various histologic clues favor a benign over a malignant mesothelial proliferation and vice versa. Invasion is the most reliable criterion for determining that a mesothelial proliferation is malignant. When there is any doubt that a pleural biopsy represents a malignancy, we recommend a diagnosis of atypical mesothelial proliferation.
Cell Proliferation and Inflammation on Biopsy Samples With Multifocal Atrophic Gastritis Before and 1 Year After Helicobacter pylori Eradication
Authors: Guarner Jeannette , Bartlett Jeanine , Seitz Roslyn , Whistler Toni , Herrera-Goepfert Roberto , Mohar Alejandro , Sanchez Luz , Halperin David , Parsonnet Julie
Published: February 2021

Context.—Results of clinical trials that have assessed whether gastric cancer is preventable with Helicobacter pylori eradication therapy remain inconclusive. These trials have used atrophy, intestinal metaplasia, and dysplasia as histopathologic end points that reflect possible preneoplastic lesions. Trial results would be more compelling if cell proliferation and inflammatory markers improved simultaneously with histopathologic lesions.

Objective.—To study the presence of cell proliferation markers and type of inflammatory cells in biopsy specimens with gastritis, atrophy, and intestinal metaplasia before and 1 year after H pylori therapy and to determine if immunohistochemistry can be used to study these.

Design.—We evaluated 12 subjects with gastritis and 16 with gastritis and multiple foci of atrophy and intestinal metaplasia by using immunohistochemical assays for tumor suppressor protein p53, proliferation marker Ki-67, cell cycle regulator cyclin D1, T and B lymphocytes, macrophages, and TUNEL (terminal deoxynucleotide transferase deoxyuridine triphosphate nick end labeling) assay for apoptosis. The biopsy specimens were selected from a randomized clinical trial that studied improvement of histopathologic gastric lesions after H pylori eradication.

Results.—Groups of surface epithelial cells that expressed p53 and Ki-67 were observed more often in subjects with atrophy and intestinal metaplasia compared with those with gastritis alone. T lymphocytes in the lamina propria were frequently observed 1 year after treatment in subjects with atrophy and intestinal metaplasia.

Conclusions.—Immunohistochemical assays for cell proliferation and inflammatory cell markers showed different distribution patterns in these gastric biopsy specimens. The presence of T lymphocytes and groups of cells that expressed proliferation markers in subjects with multiple foci of atrophy and intestinal metaplasia needs further study.
Death Certification Errors at an Academic Institution
Authors: Pritt Bobbi S. , Hardin Nicholas J. , Richmond Jeffrey A. , Shapiro Steven L.
Published: February 2021

Context.—The correctly completed death certificate provides invaluable personal, epidemiologic, and legal information and should be thorough and accurate. Death certification errors are common and range from minor to severe.

Objective.—To determine the frequency and type of errors by nonpathologist physicians at a university-affiliated medical center.

Design.—Fifty random patients were identified who died at this academic medical center between January 2002 and December 2003 and did not undergo an autopsy. From medical chart review, clinical summaries were produced. Two pathologists used these summaries to create mock death certificates. The original and mock death certificates were then compared to identify errors in the original certificate. Errors were graded on a I to IV scale, with grade IV being the most severe.

Results.—Of the 50 death certificates reviewed, grade I, II, and III errors were noted in 72%, 32%, and 30%, respectively. Seventeen certificates (34%) had grade IV errors (wrong cause or manner of death). Multiple errors were identified in 82% of the death certificates reviewed.

Conclusions.—The rate of major (grade IV) death certification errors at this academic setting is high and is consistent with major error rates reported by other academic institutions. We attribute errors to house staff inexperience, fatigue, time constraints, unfamiliarity with the deceased, and perceived lack of importance of the death certificate. To counter these factors, we recommend a multifaceted approach, including an annual course in death certification and discussion of the death certificate for each deceased patient during physician rounds. These measures should result in increased accuracy of this important document.
Nonsecretory Variant of Immunoproliferative Small Intestinal Disease: A Case Report With Pathologic, Immunophenotypic, and Molecular Findings
Authors: Pai Reetesh K. , Snider, MD Warren K. , Starkey Cindi R. , Viswanatha David , Foucar M. Kathryn , Wilson Carla S.
Published: February 2021

We report a case of the nonsecretory variant of immunoproliferative small intestinal disease involving the distal small bowel and the mesenteric and retroperitoneal lymph nodes in a 19-year-old woman from Mexico. This variant extranodal marginal zone B-cell lymphoma appeared similar in the different sites of involvement, with more interspersed large cells and greater plasmacytic differentiation present in intestinal specimens. Characteristic lymphoepithelial lesions and follicular colonization were seen in intestinal and lymph node sections, respectively. The neoplastic B cells were cytoplasmic immunoglobulin (Ig) A heavy-chain restricted and lacked surface and cytoplasmic light-chain expression by flow cytometric analysis. Serum and urine protein electrophoresis/immunofixation revealed hypogammaglobulinemia with no paraprotein. Molecular studies showed absence of immunoglobulin heavy-chain (IgH) gene rearrangement, with a nonfunctional clonotypic rearrangement of the κ light-chain gene. This case highlights the role for κ light-chain gene evaluation in immunoproliferative small intestinal disease, because IgH gene rearrangement analysis is often negative.
Do 40% of Patients Resected for Barrett Esophagus With High-Grade Dysplasia Have Unsuspected Adenocarcinoma?
Authors: Tschanz Elizabeth R.
Published: February 2021

Results of studies conducted in the last 2 decades suggest that the detection of high-grade dysplasia in patients with Barrett esophagus is the harbinger of a synchronous adenocarcinoma, which remains undetected even by rigorous biopsy protocols but is discovered during resection of the esophagus. The reported prevalence of synchronous carcinomas ranges from 0% to 75%. Other researchers maintain that appropriate surveillance programs can be used to detect carcinomas at a curable stage and to prevent unnecessary esophagectomies. Both logistical difficulties and potential methodological pitfalls have plagued many studies designed to investigate this issue. A large multicenter study that would stratify participants for hitherto unexplored variables (eg, age, gender, and ethnic background) may be required before the 40% occult cancer prevalence can be either confirmed or refuted. However, the large scale needed for such a study to provide reliable data and new developments in endoscopic imaging (eg, magnification endoscopy and optical coherence tomography) and endoscopic therapy (eg, mucosectomy) are likely to make such a study both ethically unacceptable and logistically and financially unfeasible. Future research should utilize the combination of new endoscopic technologies with the continuing search for validated biomarkers that help predict the biological behavior of Barrett epithelium in individual patients, with a particular focus on the possible development of preneoplastic and neoplastic lesions. Pathologists who chose to shift their focus from the traditional morphological investigation of dysplasia to the search for usable biomarkers can position themselves at the center of innovative research projects that could radically modify the management of patients with Barrett esophagus.
Is Adenocarcinoma of the Esophagogastric Junction or Cardia Different From Barrett Adenocarcinoma?
Authors: Ectors Nadine , Driessen Ann , De Hertog Gert , Lerut Toni , Geboes Karel
Published: February 2021

Over time the relative distribution of cancers of the proximal digestive tract has changed. Squamous cell carcinomas of the esophagus have become less common, while numbers of adenocarcinomas have greatly increased. This shift most likely reflects an increase in the incidence of gastroesophageal reflux. Moreover, there is a decline in the incidence of distal gastric cancer, which in turn may be related to Heliobacter pylori eradication. Simultaneously, there is a time trend toward a more proximal localization of gastric cancer. If the above-mentioned etiopathologic links are correct, this could indicate that the so-called cardia adenocarcinomas are not related to H pylori infection and that they may instead be related to gastroesophageal reflux and eventually may not be considered to be “gastric” cancers. The rapidly growing quantity of literature on this subject is, however, confounding. A major source of discordance would seem to be a Babylonian confusion of tongues concerning the terms cardia and cardiac carcinomas. Unfortunately, this confusion is also apparent in the classification systems available for staging of cancer, thus closing the “vicious” circle.
Rapid Quantitative Analysis of Human Cytomegalovirus DNA by the Real-Time Polymerase Chain Reaction Method
Authors: Numata Sanae , Nakamura Yasuhiro , Imamura Yutaka , Honda Junichi , Momosaki Seiya , Kojiro Masamichi
Published: February 2021

Context.—Human cytomegalovirus (CMV) infection is a progressive and life-threatening complication in immunocompromised patients even now. Therefore, early and accurate treatment based on rapid and certain detection is needed to prevent fatal CMV infection diseases.

Objective.—To study a quicker, simpler, and less expensive method of quantitative analysis using real-time polymerase chain reaction based on the SYBR Green I method of CMV detection for appropriate treatment of CMV infection in immunocompromised patients.

Design.—We quantified 50 samples tested by direct immunoperoxidase staining of leukocytes with peroxidase-labeled monoclonal antibody (C7-HRP test), 30 samples from healthy persons, and 47 samples from 7 patients suspected of having CMV infection diseases. We used the primer set in the pp65 gene of CMV and whole blood without a preparatory process. The setting for the study was the First Department of Pathology, Kurume University School of Medicine, St Mary's Hospital, and the Gene Section of the Clinical Laboratory at St Mary's Hospital, Fukuoka, Japan.

Results.—The results obtained with this method corresponded well with conventional C7-HRP tests and demonstrated excellent reproduction. Additionally, the results were better correlated with the clinical course than were C7-HRP tests.

Conclusions.—This method was more useful than the C7-HRP test as a rapid diagnostic test for early treatment of CMV infection. This test also demonstrated its usefulness for monitoring CMV infection during treatment using ganciclovir. Moreover, it was quicker, simpler, and cheaper than other real-time polymerase chain reaction methods.
Association of Drowning and Myocarditis in a Pediatric Population: An Autopsy-Based Study
Authors: Somers Gino R. , Smith Charles R. , Wilson Gregory J. , Zielenska Maria , Tellier Raymond , Taylor Glenn P.
Published: February 2021

Context.—Drowning is a frequent cause of accidental death in childhood, but the association of myocarditis and drowning has only rarely been reported.

Objective.—To report 5 cases of drowning in children with coexistent myocarditis.

Design.—A retrospective review of autopsy records of patients 0 years to 18 years of age was performed during a 6-year period (1998–2003, total cases reviewed = 1431).

Results.—Twenty-two drownings were identified, in 14 male and 8 female children. Five patients (23%), 3 female and 2 male children, had coexistent myocarditis. The 5 patients ranged in age from 23 months to 13 years (mean, 7 years 2 months). None of the patients had antecedent symptomatology suggestive of myocarditis. In all patients, the myocarditis was focal mild or moderate, and the inflammatory infiltrate comprised lymphocytes with smaller numbers of neutrophils. All 5 patients had foci of myocyte necrosis. One patient had histologic evidence of myocardial hypertrophy but no evidence of a cardiomyopathy. Microbiologic studies, including culture, immunohistochemistry, polymerase chain reaction, and reverse transcriptase polymerase chain reaction, revealed Mycoplasma pneumoniae DNA in 1 case.

Conclusions.—The finding of myocarditis in a significant proportion of drowning victims in this series highlights the importance of a thorough autopsy examination in apparently straightforward cases and has clinicopathologic significance.