bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Invasion in the Excision Specimen From Breast Core Needle Biopsy Specimens With Only Ductal Carcinoma In Situ
Authors: Renshaw Andrew A.
Published: January 2021

Objective.—Some patients with ductal carcinoma in situ on breast core needle biopsy will have invasion at excision. The aim of this study was to determine if patients at increased risk for invasion could be identified.

Methods.—The results of all breast core needle biopsies with a diagnosis of ductal carcinoma in situ during a 50-month period were reviewed. A variety of histologic features were identified and correlated with the presence of invasion at excision.

Results.—Of 3026 cases, 152 (5%) were diagnosed as ductal carcinoma in situ; excisional biopsies were available for 91 (60%) of these 152 cases, and 17 (19%) showed invasive tumor. Neither the radiographic findings, presence of comedonecrosis, comedo histology, lobular extension, size of the largest focus, nor aggregate size was significantly associated with an increased incidence of invasion (all P > .05). However, comedo histology with a cribriform/papillary architecture was significantly associated with an increased risk of invasion (5/7 [72%] cases with invasion, P = .002), as were tumors greater than 4 mm with lobular extension (6/15 [40%], P = .03).

Conclusion.—Patients with comedo ductal carcinoma in situ with a cribriform/papillary pattern or tumor involving more than 4 mm with lobular extension in breast core needle specimens are at increased risk for invasion at excision.
Squamous Cell Carcinomas Arising From Adnexal Ductal Cysts
Authors: Skelton Henry G. , Flax Steven , Chang Lawrence , Smith Kathleen J.
Published: January 2021

Malignant tumors arising from adnexal cysts are rare. We report 2 cases of squamous cell carcinomas that developed within cystic structures arising from adnexal ducts. An in situ hybridization technique for human papillomaviruses (HPV)-6/11, -16, -18, and -31, and immunohistochemical staining for p53 were performed. Both tumors showed focal expression of HPV-16 within areas showing squamoid changes and diffuse expression of p53 within the areas of invasive squamous cell carcinoma. Although nuclear staining for HPV has been identified in tumors of adnexal origin, to our knowledge these are the first cases in which a highly oncogenic HPV subtype, HPV-16, has been identified within squamous cell carcinomas arising from adnexal ductal structures. These cases may help explain primary cutaneous squamous cell carcinomas with no epidermal origin.
Livebirths With Placental Hemorrhagic Endovasculitis
Authors: Sander C. Maureen , Gilliland Dennis , Akers Cheryl , McGrath Ann , Bismar Tarek A. , Swart-Hills Laura A.
Published: January 2021

Background and Objective.—Hemorrhagic endovasculitis (HEV) is a vasodisruptive alteration of fetal-placental blood vessels that has been associated with perinatal morbidity and mortality and abnormalities of growth and development. Clinicopathologic conditions that are often identified in pregnancies with HEV-affected placentas include villitis of unknown etiology, chorionic vessel thrombi, villous erythroblastosis, meconium staining, and maternal hypertension. The clinical implications of HEV are often disputed. This case-control study assesses the clinical relevance of HEV in placentas of viable infants and examines the interplay of coexistent intraplacental lesions.

Methods.—We reviewed clinical records and slides from 104 livebirths with placentas affected by HEV above a specified severity level (cases) and 104 matched livebirths with placentas that were not affected by HEV (controls). We evaluated incidences of perinatal complications with increasing HEV severity indices in placentas with and without coexistent lesions. Interlesional relationships were established by matching HEV severity indices with severity indices of coexistent lesions. Hemorrhagic endovasculitis was subcategorized into active, bland, and healed forms and clustered capillary lesions (hemorrhagic villitis).

Results.—Lesions that were frequently coexistent in HEV-affected placentas included villitis of unknown etiology, chorionic thrombi, villous fibrosis, erythroblastosis, and primary infarcts. Compared with the control group, the case group had higher incidences of abnormal fetal heart rate tracings (P < .003), fetal distress (P < .001), and growth restriction (P < .001). Increasing severities of HEV and coexistent lesions were associated with higher rates of perinatal complications. Complication rates were higher in HEV cases, with or without coexistent lesions. The complication rate was higher in cases affected by HEV and hemorrhagic villitis than in cases affected by HEV alone (P < .03). Significant interlesional relationships were evident between HEV and villitis of unknown etiology, chorionic thrombi, villous fibrosis, and erythroblastosis.

Conclusions.—Severe forms of HEV can occur in placentas of livebirths. The severity of HEV and associated lesions and the presence of hemorrhagic villitis have important clinical implications. Interlesional relationships between HEV and thrombotic, chronic inflammatory, and chronic vaso-occlusive lesions exist. Pregnancies with HEV-affected placentas with or without coexistent lesions are at risk for perinatal complications.
The Use of TaqMan PCR Assay for Detection of Bordetella pertussis Infection From Clinical Specimens
Authors: Chan Edward L. , Antonishyn Nick , McDonald Ryan , Maksymiw Tara , Pieroni Peter , Nagle Evelyn , Horsman Greg B.
Published: January 2021

Objective.—The routine clinical laboratory detection of Bordetella pertussis is through culture, which can require 5 to 7 days for the bacteria to grow. Using a polymerase chain reaction (PCR) assay can shorten this detection time while increasing the sensitivity of detection with similar specificity. This study compared culture with TaqMan PCR for detection of B pertussis in clinical specimens and the turnaround time for each assay during the pertussis season.

Materials and Methods.—Nasopharyngeal swabs in Regan-Lowe transport media were collected from 1556 persons who had symptoms of whooping cough or who had had contact with infected persons; the swabs were submitted for B pertussis detection during the pertussis season. A single nasopharyngeal swab from each patient was submitted for both culture and TaqMan PCR detection. Upon receipt of the specimens, the swabs were inoculated onto Regan-Lowe agar for culture and incubated for up to 7 days. The same swab was processed for PCR detection using TaqMan PCR assay. A second nested PCR was used on positive specimens for resolution purposes. The TaqMan PCR assay was performed 3 to 5 days a week, whereas the culture was performed 6 days a week. All specimens were processed on the same day or earliest possible working day for TaqMan or culture, and specimens queued for resolution by nested PCR were batched.

Results.—There were a total of 275 PCR positives and 28 culture positives. After resolution with the second nested PCR, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 97.4%, 87.6%, and 100% for TaqMan PCR and 11.6%, 100%, 100%, and 85.7% for culture. The average turnaround time for positive culture was 5.1 days, and the average turnaround time for PCR was 2.3 days.

Conclusion.—The TaqMan PCR assay has superior sensitivity and shorter turnaround time over culture because it can be finished within one working day. Furthermore, the same swab can be used for culture of the bacteria for antibiotic susceptibility testing. The early detection of pertussis using TaqMan PCR assay allows early intervention on the spread of the disease and the ability to culture the bacteria from the same swab, thereby eliminating the need for a second swab and allowing for detection of antibiotic resistance.
Utilizing Genomic DNA Purified From Clotted Blood Samples for Single Nucleotide Polymorphism Genotyping
Authors: Adkins Karissa K. , Strom Daniel A. , Jacobson Thomas E. , Seemann Cara R. , O'Brien Darin P. , Heath Ellen M.
Published: January 2021

Context.—Linking single nucleotide polymorphisms to disease etiology is expected to result in a substantial increase in the number of genetic tests available and performed at clinical laboratories. Whole blood serves as the most common DNA source for these tests. Because the number of blood samples rises with the number of genetic tests performed, alternative DNA sources will become important. One such alternative source is clotted blood, a by-product of serum extraction. Efficiently using an already procured blood sample would limit the overall number of samples processed by clinical laboratories.

Objective.—To determine if DNA purified from clotted blood can be effectively used for single nucleotide polymorphism genotyping.

Design.—DNA was purified from the clotted blood of 15 donors. Single nucleotide polymorphism genotyping for the methylenetetrahydrofolate reductase and factor V Leiden mutations was performed with each DNA sample by 2 independent methods.

Results.—High-quality DNA was obtained from each of the 15 individual clotted blood samples as demonstrated by UV spectrophotometric analysis, gel electrophoresis, and polymerase chain reaction amplification. The DNA was used successfully to obtain genotype data from both the methylenetetrahydrofolate reductase and factor V single nucleotide polymorphism assays for all samples tested.

Conclusions.—Clotted blood is a clinically abundant sample type that can be used as a source of high-quality DNA for single nucleotide polymorphism genotyping.
Molecular Testing in the Diagnosis and Management of Hepatitis C Virus Infection
Authors: Podzorski Raymond P.
Published: January 2021

Objectives.—To review hepatitis C virus (HCV), describe the types of molecular-based tests available for the diagnosis and management of HCV infection, and discuss the appropriate utilization of these tests.

Data Sources.—Current information is presented from the published literature, as well as new information where available.

Study Selection.—A major cause of posttransfusion and community-acquired non-A, non-B hepatitis worldwide is HCV. Approximately 4 million people in the United States are infected with HCV, resulting in 8000 to 10 000 deaths annually. Because HCV is not readily cultured, in vitro molecular-based tests have been developed for use in the diagnosis and treatment of HCV-infected patients. Molecular tests include qualitative and quantitative nucleic acid amplification tests, branched DNA tests, and HCV genotyping assays. Qualitative HCV nucleic acid amplification tests are used routinely in association with serologic tests to help make a diagnosis of infection with HCV. Quantitative HCV testing and genotyping methods have been found to be valuable tools in the treatment of infected patients. A patient's pretreatment HCV viral load and the rate of virus decline during therapy have been shown to correlate with the likelihood of long-term response to antiviral therapy. Information pertaining to the genotype of HCV infecting patients has been shown to be helpful in making recommendations regarding treatment. Certain genotypes of HCV are much more responsive to therapy, allowing a shorter course of treatment.

Conclusions.—Molecular tests are valuable tools for use in the diagnosis and treatment of patients infected with HCV.
Postmortem Diagnosis of “Occult” Klinefelter Syndrome in a Patient With Chronic Renal Disease and Liver Cirrhosis
Authors: Matsuoka Kentaro , Orikasa Hideki , Eyden Brian , Yamazaki Kazuto
Published: January 2021

This report describes a patient not suspected of having Klinefelter syndrome during life but diagnosed with it following postmortem examination using fluorescent in situ hybridization (FISH) for sex chromosomes and hormone serum analysis. A 49-year-old Japanese man had a history of nephrosis, heavy alcohol consumption, diabetes mellitus, and liver cirrhosis and had been undergoing dialysis for 10 years. He died of ruptured esophageal varices. Autopsy revealed hypogonadism, suggesting Klinefelter syndrome. This was confirmed by FISH, which showed a mosaic 46XY, 47XXY karyotype, and by serum analysis, which revealed high luteinizing hormone and follicle-stimulating hormone and low testosterone levels. Autopsy also revealed a nodular, bilateral, testicular Leydig cell hyperplasia. This report illustrates the value of postmortem laboratory investigations, particularly FISH for sex chromosomes and serum hormone analysis, for the demonstration of clinically uncertain or “occult” Klinefelter syndrome.
Altered Expression of G1 Regulatory Proteins in Human Soft Tissue Sarcomas
Authors: Yoo Jinyoung , Park Sonya Y. , Kang Seok Jin , Shim Sang In , Kim Byung Kee
Published: January 2021

Context.—Soft tissue sarcomas constitute a heterogeneous group of tumors for which tumorigenesis is not fully understood. Altered cell-cycle regulation may underlie the development and/or progression of human malignancies. However, data concerning the occurrence of cell-cycle aberrations in soft tissue sarcomas are very limited.

Objectives.—To detect the abnormal features of cell-cycle regulatory proteins in soft tissue sarcomas and to determine the potential role of these proteins in clinical behavior.

Design.—The p53 and Rb–cyclin D pathways were investigated by immunohistochemical studies of p53, mdm2, pRb, p16, cyclin D1, and cdk4 proteins, respectively.

Results.—Of the 67 sarcomas analyzed, nuclear accumulation of p53 was detected in 25 samples (37%), and overexpression of mdm2 was found in 16 samples (24%). Both p53 and mdm2 expression correlated with tumor grade. Abnormalities involving the Rb–cyclin D pathway were identified in all of the tumors by the altered expression of either pRb (72%) or p16 (94%). Fourteen (21%) and 64 (96%) cases demonstrated cyclin D1 or cdk4 expression, respectively. Overexpression of cyclin D1 showed an association with pRb and p53. There was no correlation between pRb, p16, cyclin D1, or cdk4 and tumor grade or relapse.

Conclusion.—Disturbance in the cell-cycle regulatory system involving the p53 pathway and the Rb–cyclin D pathway is relatively frequent in soft tissue sarcomas and may be a contributing factor in the tumorigenesis of these tumors. The alterations in the Rb–cyclin D pathway probably constitute an early event, whereas the abnormalities in the p53 pathway seem to be involved in tumor progression. It is noteworthy that cyclin D1 may play a key role in linking both pathways.
Detection of bcl-2/JH Translocation by Polymerase Chain Reaction
Authors: Hsi Eric D. , Tubbs Raymond R. , Lovell Mark A. , Braziel Rita M. , Gulley Margaret L.
Published: January 2021

Context.—The t(14;18)(q32;;t6q21) translocation, found in about 85% of follicular lymphomas, brings the bcl-2 gene on 18q21 under control of the immunoglobulin heavy-chain gene transcriptional regulatory elements on 14q32. Detection of this translocation in a clinical sample suspected of containing lymphoma can assist the pathologist in diagnosis and classification of lymphoma. Polymerase chain reaction is a technology that is frequently used to detect the t(14;18)(q32;q21) translocation (bcl-2/JH). This article reviews the utility of polymerase chain reaction testing for bcl-2/JH detection and summarizes the experience of participants in the Molecular Oncology Proficiency Survey of the College of American Pathologists from 1997 through 2000.

Objective.—To describe current practice and encourage improvement of bcl-2/JH testing in clinical laboratories.

Design.—Retrospective analysis of Molecular Oncology Proficiency Survey data.

Participants.—Laboratory participants in the College of American Pathology Molecular Oncology Proficiency Survey.

Results.—Twenty-four well-characterized specimens were sent to participants, of which 6 contained bcl-2/JH major breakpoint region translocations. Eight hundred nineteen major breakpoint region and 323 minor cluster region determinations were performed, with an overall correct response rate of 91% and 94%, respectively. No significant difference in correct response could be found for frozen versus paraffin-embedded tissues. Many laboratories did not know their assay sensitivity.

Conclusions.—Overall performance was good; however, there was great variability in the methods reported and lack of knowledge of the limits of detection was common. Continued participation in external quality control programs, such as the Molecular Oncology Survey; dissemination of information that impacts on test performance; and technical recommendations from the molecular diagnostics community are critical for improved testing for bcl-2/JH.
Blinded Review as a Method for Quality Improvement in Surgical Pathology
Authors: Renshaw Andrew A. , Pinnar Nat E. , Jiroutek Michael R. , Young Mary L.
Published: January 2021

Context.—Several studies have shown that blinded review, because it is less biased and may improve vigilance, is an excellent method for detecting errors and improving performance in gynecologic cytology. The value of blinded review in surgical pathology is not known.

Objective.—To determine the value of blinded review in surgical pathology.

Methods.—Five hundred ninety-two biopsy cases were reviewed without knowledge of the original diagnosis or history, and the results were compared with those of the original diagnosis.

Results.—Complete agreement was obtained in 567 (96%) of 592 cases. The technique of blinded review of biopsy material had a sensitivity of 98%, failing to identify a lesion in 7 cases; no cases of malignancy were missed. The specificity was 100%. Differences in diagnostic threshold were the most common source of disagreement. False-negative cases were identified by the technique and were clinically significant. Power studies show that the number of cases requiring review to identify significant errors are large, but potentially achievable by blinded review.

Conclusion.—Blinded review is a sensitive and effective method for identifying areas of disagreement, including false-negative cases, and for decreasing errors in surgical pathology biopsy material.
A Malignant Gastrointestinal Stromal Tumor With Osteoclast-like Giant Cells
Authors: Leung Kai Man , Wong Shun , Chow Tat Chong , Lee Kam Cheong
Published: January 2021

Gastrointestinal stromal tumors (GISTs) are a heterogeneous group of mesenchymal tumors with a wide spectrum of histologic features and consistent expression of c-Kit. We describe an 85-year-old woman who presented with left lower quadrant abdominal pain and was subsequently diagnosed as having a malignant GIST. The tumor was composed of short fascicles of spindle cells. In addition to the presence of tumor giant cells, the tumor also demonstrated many osteoclast-like giant cells, a feature that has not been previously described in the literature. These giant cells expressed histiocytic markers CD68 and α1-antitrypsin but not c-Kit, a marker for GISTs. Electron microscopy showed no features of smooth muscle differentiation in the giant cells. The possible origin of the osteoclast-like giant cells is discussed in the context of immunohistochemical and ultrastructural characteristics.
Hibernoma
Authors: Lele Subodh M. , Chundru Satish , Chaljub Gregory , Adegboyega Patrick , Haque Abida K.
Published: January 2021

Hibernomas are rare neoplasms composed of brown adipose tissue. The behavior of these neoplasms has been described as uniformly benign in humans. The only recurrence cited in the English literature involved a sarcoma with hibernoma-like features, which was reported in abstract form. We present 2 cases of hibernoma, one that continued to grow following partial excision and another at an unusual site (anterior abdominal wall). Both of these tumors overexpressed p53 protein by immunohistochemistry, which was a novel finding. A review of the literature highlights recent advances that may help confirm the diagnosis and explain the biology of these rare tumors.
The Role of the Autopsy in Medical Malpractice Cases, II
Authors: Bove Kevin E. , Iery Clare
Published: January 2021

Context.—We studied 99 appellate court records in cases of alleged medical malpractice and found no relationship between discrepant clinical and autopsy findings and outcome of litigation. Standard-of-care issues and not diagnostic accuracy were at the heart of every case.

Objective.—To characterize and discuss issues related to the autopsy and/or pathologist behavior that were raised in court records of medical malpractice litigation.

Design.—In 18 appellate court records, issues were raised about quality of autopsy performance and reporting or about death certification. The details of these controversies are succinctly reported here in a manner intended to be instructive to pathologists who perform autopsies in a hospital setting or on a private fee-for-service basis.

Conclusion.—Autopsy reports are intended to provide objective medical information in a coherent format to the patient's medical record, to the attending physician and other concerned staff physicians, to other health care professionals, and to the families of the deceased. Inevitably, occasions arise that require legal counsel to be added to this list of parties with a legitimate interest. Our findings emphasize that incomplete, incoherent, obfuscated, or delayed reporting of autopsy findings do not meet professional standards, are unethical if intentional, and may be counterproductive.
Immunohistochemical Confirmation of Pulmonary Papillary Adenocarcinoma Metastatic to Ovaries
Authors: Householder Jean Marie , Han Aaron , Edelson Mitchell I. , Eager J. Michael , Rosenblum Norman G.
Published: January 2021

Metastatic papillary adenocarcinomas of the ovary are rare compared to primary ovarian papillary serous carcinomas. We report a case of pulmonary papillary adenocarcinoma metastatic to the ovary and show how this tumor can be differentiated immunohistochemically from an ovarian primary. Paraffin blocks of the ovarian tumor were analyzed for carcinoembryonic antigen, CA 125, surfactant, E-cadherin, N-cadherin, and vimentin. These markers are useful in differentiating epithelial tumors of lung versus ovarian origin. The papillary tumor showed expression of carcinoembryonic antigen, surfactant, and E-cadherin, but was negative for CA 125, N-cadherin, and vimentin. These findings support a lung carcinoma metastatic to the ovary.
Malignant Melanoma of the Oral Mucosa in a 17-Year-Old Adolescent Girl
Authors: D'Silva Nisha J. , Kurago Zoya , Polverini Peter J. , Hanks Carl T. , Paulino Augusto F.
Published: January 2021

Mucosal melanomas of the oral cavity are rarely seen in the United States. The hard palate is the most common intraoral site. This unusual case occurred in the oral cavity of a 17-year-old Asian girl, who presented to her dentist with complaints of pain and swelling in the upper jaw. The lesion was distal and palatal to the maxillary left second molar, which was vital. Interestingly, the clinical presentation was a hyperplastic, tender lesion that bled when probed. Histopathologically, the biopsy demonstrated a sheet of spindle-shaped cells arranged in nests and fascicles. The nuclei were vesicular, oval to spindle-shaped, and some contained nucleoli that were distinguishable but not prominent. No melanin pigment was observed in the lesion. Tumor cells strongly expressed S100 protein, gp100 (HMB-45), and microphthalmia transcription factor, and variably expressed MART1, but not cytokeratins, CD34, or muscle-specific actin. The histopathologic features and immunohistochemical findings are consistent with a diagnosis of malignant melanoma.
Carcinosarcoma of the Pancreas
Authors: Darvishian Farbod , Sullivan James , Teichberg Saul , Basham Kevin
Published: January 2021

We report the case of a 74-year-old white man with a mass in the head of the pancreas, which was found incidentally on computerized tomographic scan during a workup for deep vein thrombosis. Endoscopy with pancreatic duct brushings yielded a diagnosis of adenocarcinoma. A pancreaticoduodenectomy followed, with complete resection of the tumor. Pathologic examination showed 2 distinct components. One component was a conventional infiltrating pancreatic ductal adenocarcinoma, and the other component was high-grade sarcoma with features of malignant fibrous histiocytoma. To our knowledge, this carcinosarcoma is the seventh reported case of a primary pancreatic neoplasm with mixed carcinomatous and sarcomatous elements.
College of American Pathologists Consensus Conference XXXVI: Diagnostic Issues in Thrombophilia
Authors: Olson John D.
Published: January 2021

Objectives.—To review the state of the art relating to laboratory testing for thrombophilia, as reflected by the medical literature and the consensus opinion of recognized experts in the field, and to make recommendations regarding laboratory testing (whom to test, when to test, what tests to perform, rationale for testing, and other issues) in the assessment of thrombotic risk in individual patients and their family members.

Data Sources.—Review of the medical literature (primarily from the last 10 years) and the experience and opinions of experts in the field were used as data sources.

Data Extraction and Synthesis.—Participating authors evaluated the medical literature and prepared manuscripts with specific proposed recommendations. Drafts of all of the manuscripts were prepared and circulated to every participant in the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia prior to the conference. Each of the conclusions and associated recommendations was then presented for discussion. Recommendations were accepted if a consensus of 70% or more of the 27 experts attending the conference was reached. The results of the discussion were then used to revise the manuscripts and recommendations into final form.

Conclusions.—Consensus was reached on 179 recommendations, all of which are presented in articles in this issue of the Archives. Detailed discussion of the rationale for each of these recommendations is found in the text of the respective articles, along with citations to justify the level of evidence for the recommendations. This is an evolving area of research, and it is certain that further clinical studies will change many of the recommendations, cause some to be deleted, and add others in the future.
Dysfibrinogenemia and Thrombosis
Authors: Hayes Timothy
Published: January 2021

Objectives.—To review the state of the art relating to congenital dysfibrinogenemia as a potential risk factor for thrombosis, as reflected by the medical literature and the consensus opinion of recognized experts in the field, and to make recommendations for the use of laboratory assays for assessing this thrombotic risk in individual patients.

Data Sources.—Review of the medical literature, primarily from the last 10 years.

Data Extraction and Synthesis.—After an initial assessment of the literature, key points were identified. Experts were assigned to do an in-depth review of the literature and to prepare a summary of their findings and recommendations. A draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia. Each of the key points and associated recommendations were then presented for discussion at the conference. Recommendations were accepted if a consensus of experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form.

Conclusions.—Consensus was reached on 5 conclusions and 2 recommendations concerning the use of testing for dysfibrinogens in the assessment of thrombotic risk in individual patients. Detailed discussion of the rationale for each of these recommendations is found in the text of this article. Compared with the other, more common hereditary thrombophilias, dysfibrinogenemia encompasses a diverse group of defects with varied clinical expressions. Congenital dysfibrinogenemia is a relatively rare cause of thrombophilia. Therefore, routine testing for this disorder is not recommended as part of the laboratory evaluation of a thrombophilic patient. This is an evolving area of research, and further clinical studies may change these recommendations in the future.
Alzheimer Pathology in Elderly Patients With Glioblastoma Multiforme
Authors: Nelson James S.
Published: January 2021

Context.—Alzheimer disease (AD) and glioblastoma multiforme (GBM) have similar peak, age-specific incidence rates; however, to my knowledge, only 1 case of GBM associated with AD has been reported to date. The frequency of AD pathology, including neuritic plaques, diffuse plaques, neurofibrillary tangles, and cerebral amyloid angiopathy in patients with GBM is unknown. Studies of cancer occurrence in patients with AD are contradictory, with frequencies reported as equal to and as less than that in the general population. The GBM/AD nonconcordance may reflect underreporting of AD pathology or other factors.

Objective.—To compare the frequency and extent of neocortical AD pathology in autopsy cases involving patients aged 60 to 82 years, both with and without GBM.

Design.—Case-control study.

Setting.—Pathology department of a university hospital.

Patients.—Thirty-six autopsy cases of GBM patients aged 60 to 82 years; 54 cases of patients in the same age group without GBM or other primary brain tumors.

Methods.—Examination of tumor sections for GBM and of neocortical sections for AD pathology according to Consortium to Establish a Registry for Alzheimer Disease (CERAD) guidelines.

Results.—Glioblastoma multiforme was confirmed in all tumor cases. Alzheimer disease pathology was present in 42% of cases with GBM and in 48% of cases without GBM; 28% of GBM cases had CERAD age-related plaque scores indicative or suggestive of AD; 43% of cases without GBM had CERAD age-related plaque scores indicative or suggestive of AD.

Conclusions.—Alzheimer disease pathology was underreported in both GBM and non-GBM patients. The influence of neurodegenerative processes on GBM symptoms and therapy in elderly patients requires further study.
Testicular Natural Killer/T-Cell Lymphoma, Nasal Type, of True Natural Killer–Cell Origin
Authors: Totonchi Kameel F. , Engel George , Weisenberg Elliot , Rhone Douglas P. , Macon William R.
Published: January 2021

The majority of primary testicular lymphomas are of B-cell type. Other primary lymphomas are rarely encountered in the testes. Natural killer (NK)/T-cell lymphomas of nasal type are aggressive extranodal lymphomas associated with Epstein-Barr virus infection that are usually encountered in the upper aerodigestive tract. They also occur in the skin, soft tissue, and colon. Primary testicular NK/T-cell lymphomas are rarely reported. We describe the case of a 66-year-old Korean man who presented with right-sided painless testicular enlargement and underwent radical orchiectomy. Histologic examination revealed an angiocentric and angioinvasive infiltrate of medium to large tumor cells with moderately abundant pale pink cytoplasm and folded and indented pleomorphic nuclei. Paraffin immunohistochemical studies showed positivity of the tumor cells for CD45, TIA-1, granzyme B, CD56, and CD3ɛ. In situ hybridization showed diffuse positivity for Epstein-Barr virus–encoding RNA. The results of gene rearrangement studies for the γ chain of the T-cell receptor were negative. The results of paraffin immunohistochemical studies for CD20, CD8, CD45RO, beta f1, and ALK-1 were negative. An extensive workup showed no evidence of lymphoma outside the testes. We report a rare case of primary testicular NK/T-cell lymphoma of the nasal type of true NK-cell origin.
Primary Gastroesophageal-Ileal Hodgkin Lymphoma
Authors: Perez Maria T. , Cabello-Inchausti Beria , Castellano-Sanchez Amilcar , Kottiech Samer , Davila Enrique , Willis Irvin , Barkin Jamie
Published: January 2021

Primary Hodgkin lymphoma of the gastrointestinal tract is exceedingly rare to the point that some authors regard with skepticism the existence of this entity. Cases of gastrointestinal Hodgkin lymphoma have been reported previously; however, most of these cases represented secondary involvement of the digestive tract in the context of systemic disease. Other cases have been reclassified in retrospective studies as non-Hodgkin lymphomas after the application of immunohistochemical techniques. We report a case of primary Hodgkin lymphoma of the gastrointestinal tract in a patient who presented with obstructive symptoms at the site of a gastroileal bypass; the bypass had been performed years earlier because of morbid obesity. Some non-Hodgkin lymphomas may morphologically mimic Hodgkin lymphoma and vice versa; therefore, an accurate pathologic diagnosis is important, since the therapeutic approach and prognostic implications differ significantly for these diseases. In this context, immunohistochemistry should be used to confirm or to exclude the histologic diagnosis of Hodgkin lymphoma.
A Longitudinal Replicate Study of Immunosuppressive Drugs
Authors: Steele Bernard W. , Wang Edward , Soldin Steven J. , Klee George , Elin Ronald J. , Witte David L.
Published: January 2021

Objective.—To identify the sources of analytical variation for cyclosporine and tacrolimus in a 3-year longitudinal study.

Design.—Two pools of whole blood were spiked with cyclosporine and tacrolimus, respectively. One aliquot of cyclosporine and 2 of the tacrolimus pool were distributed in the first and last mailing for years 1999 to 2001. For both drugs, the total variance for each method was partitioned into within- and between-laboratory components.

Setting.—The A and C mailings of the 1999, 2000, and 2001 AACC/CAP [American Association for Clinical Chemistry/College of American Pathologists] Immunosuppressive Drugs (CS) Monitoring Survey.

Main Outcome Measures.—For each drug, total variance was partitioned into specimen, mailing, year, and interlaboratory effects for each analytical method.

Participants.—The 292 laboratories for cyclosporine and 177 laboratories for tacrolimus enrolled in the survey from 1999 to 2001.

Results.—For both cyclosporine and tacrolimus, the major source of imprecision came from within-laboratory factors, which accounted for nearly 85% (range, 77% to 90%) of the total variance. For cyclosporine, the major component of within-laboratory variance was between-mailing, within-year effect, whereas for tacrolimus it was the between-year, within-laboratory variation.

Conclusion.—The major source of long-term survey imprecision for cyclosporine and tacrolimus is within-laboratory factors. The finding that 85% of the total variance was due to within-laboratory variation is similar to other therapeutic drugs.
Pulmonary Sclerosing Hemangioma With Lymph Node Metastases
Authors: Miyagawa-Hayashino Aya , Tazelaar Henry D. , Langel Desiree J. , Colby Thomas V.
Published: January 2021

Context.—Sclerosing hemangioma is an unusual pulmonary tumor. Previously, 4 patients with pulmonary sclerosing hemangioma and lymph node metastases have been described in the literature.

Objective.—To report 4 additional cases of metastatic sclerosing hemangioma.

Design.—Retrospective review of the authors' consultation files and review of histologic sections of pulmonary tumors and lymph node metastases.

Results.—Four cases of a morphologically benign pulmonary sclerosing hemangioma with regional lymph node metastases (including hilar, peribronchial, and interlobar metastases) were identified. The patients (3 female, 1 male) had a mean age of 39 years (range, 10–56 years). The tumors ranged in size (greatest dimension) from 1.5 to 4.7 cm (mean, 3.1 cm). The pulmonary tumors were typical circumscribed sclerosing hemangiomas without mitotic activity, angiolymphatic invasion, or necrosis. One tumor had focal cytologic atypia. The metastases were identified in hilar lymph nodes that were removed at operation for the lung nodule. One patient received adjuvant chemotherapy for adenocarcinoma. All of the patients are alive. No recurrences or residual disease has been detected at a mean follow-up of 4.7 years (range, 2.3–10 years).

Conclusions.—On the basis of case data from the 4 patients described here and the 4 patients described previously, metastases to regional lymph nodes from pulmonary sclerosing hemangioma may occur but are rare and do not appear to affect prognosis.
Biphenotypic Acute Leukemia With Coexpression of CD79a and Markers of Myeloid Lineage
Authors: Frater John L. , Yaseen Nabeel R. , Peterson Lo Ann C. , Tallman Martin S. , Goolsby Charles L.
Published: January 2021

Acute leukemias demonstrating immunophenotypic features of more than 1 cell lineage are referred to as acute leukemias of ambiguous lineage in the new World Health Organization classification system. A subtype of leukemia of ambiguous lineage is biphenotypic acute leukemia in which the malignant cell population expresses markers of 2 different lineages, most commonly myeloid and either B- or T-lymphoid lineages. This entity has been defined by a scoring system proposed by the European Group for the Immunological Characterization of Acute Leukemias (EGIL), with various markers assigned a score of 2, 1, or 0.5 depending on their specificity for myeloid or lymphoid lineage. Those cases having a score greater than 2 for the myeloid and either the B- or T-lymphoid lineages are biphenotypic acute leukemia in this system. One marker, CD79a, has been so clearly associated with acute lymphoblastic leukemia (ALL) by some researchers that its expression in the presence of blast markers is considered indicative of B-ALL. We describe an unusual case of acute leukemia meeting the criteria for biphenotypic acute leukemia in which CD79a expression was observed in the blast population.
Hepatocellular Injury With Hyperaminotransferasemia After Cresol Ingestion
Authors: Kamijo Yoshito , Soma Kazui , Kokuto Mikio , Ohbu Makoto , Fuke Chiaki , Ohwada Takashi
Published: January 2021

A 42-year-old man attempted suicide by ingesting about 150 mL of a saponated cresol solution containing about 50% cresol. His serum aminotransferase concentrations were elevated, and a coagulopathy was present at the time of admission, 15 hours after ingestion. The hyperaminotransferasemia and coagulopathy worsened on the second day, but resolved thereafter with supportive therapy. Histologic examination of a biopsy specimen obtained on the 14th day demonstrated focal dropout of hepatocytes (which were replaced by reticulin and collagen fibers), ballooning or hydropic degeneration of hepatocytes, and rapid regeneration with small hepatocytes in the periportal zones as well as in the centrilobular zones. A rapid onset of illness with periportal hepatocellular injury is inconsistent with damage due to a hepatotoxic metabolite of p-cresol produced by cytochrome P450, which has been suggested by studies in vitro. A direct transient noxious effect mediated via the portal or arterial circulation may be involved in hepatic injury after cresol ingestion.
Secondary Amyloidosis and Gastrointestinal Stromal Tumors
Authors: Overstreet Kerith , Barone Robert M. , Robin Howard S.
Published: January 2021

A 69-year-old man presented with a malignant gastrointestinal stromal tumor associated with secondary amyloidosis. The tumor had classic features of a malignant gastrointestinal stromal tumor with interlacing fascicles and whorls of spindled cells, numerous and conspicuous mitotic figures, and extensive coagulative necrosis. The cells stained diffusely for CD117 (c-Kit), confirming the diagnosis of gastrointestinal stromal tumor. The spleen, 1 adrenal gland, and part of the pancreas were removed en block with the stomach. By microscopy, the spleen and adrenal gland were partially replaced with amyloid deposits confirmed by Congo red staining, electron microscopy, and immunohistochemistry. In contrast, neither the tumor nor the surrounding vasculature showed amyloid deposition. To our knowledge, this represents only the second case of systemic amyloidosis associated with a gastrointestinal stromal tumor. This case is unique in that extensive, diffuse amyloid deposits were observed in the spleen, adrenal gland, and liver.
Giant Fibrovascular Polyp of the Esophagus
Authors: Fries Matthew R. , Galindo Rene L. , Flint Paul W. , Abraham Susan C.
Published: January 2021

Giant fibrovascular polyp of the esophagus is a rare but dramatic entity. These large polyps arise in the proximal esophagus and can cause airway obstruction secondary to mechanical pressure on the larynx, or they can present as a mass that is regurgitated into the oral cavity. We present a 66-year-old man who complained of nausea and vomiting that were associated with a fibrovascular polyp protruding into the mouth. He had also experienced several episodes of syncope resulting from intermittent airway obstruction. He underwent an open resection of an 11.8-cm fibrovascular polyp and an endoscopic resection of a second fibrovascular polyp 2 days later. Histopathologically, both masses were composed of a mixture of mature adipose tissue lobules and fibrovascular tissue, lined by reactive squamous epithelium. Despite their large size, giant fibrovascular polyps should be recognized radiologically and pathologically as benign lesions. However, they can result in significant morbidity.
Non–Acquired Immunodeficiency Syndrome-Defining Malignancies in Patients Infected With Human Immunodeficiency Virus
Authors: Demopoulos Byron P. , Vamvakas Eleftherios , Ehrlich Jacqueline E. , Demopoulos Rita
Published: January 2021

Context.—Non–acquired immunodeficiency syndrome (AIDS)-defining malignancies that occur in patients infected with human immunodeficiency virus (HIV) and the demographics and pathologic features associated with these malignancies have not been completely defined.

Objective.—This study describes the age of onset of malignant disease in patients seropositive for HIV and in control patients presumed to be negative for HIV, but with the same primary site. We compare the demographics and histopathology for both groups.

Design.—From 1993 to 1997, 57 cases involving HIV-positive patients with malignancies from 16 primary sites were recorded in the Cancer Registry files at Bellevue Hospital; 519 cases involving patients negative for HIV were recorded during this same period. We compared the age at diagnosis, sex, race, tumor histology, stage, and grade between these 2 groups.

Results.—The average age of HIV-positive patients was 47.6 years, compared with 60.3 years in the control group (P < .001). When the 16 cancer sites were compared individually, HIV-positive patients were significantly younger at onset of lung (HIV-positive patients/control group) (19/245), skin (11/77), penile (3/5), laryngeal (3/18), tongue (5/16), and colorectal (2/38) carcinomas. Patients infected with HIV had a more frequent history of smoking (41/328; P = .04) and illicit drug use (30/49; P < .001). The HIV-positive patients also were found to have a lower clinical stage of disease, compared with controls, largely due to the higher prevalence of stage 0 tumors (13/46; P = .01).

Conclusions.—The finding of younger age at diagnosis in HIV-positive compared to presumed HIV-negative patients may be related in part to earlier detection, as well as preexisting immunosuppression. The specific sites for which a significant difference in age between the HIV-positive and control cases was observed may be related to the mechanisms of immunosurveillance in parts of the body that have ready access to the outside environment. Knowledge of younger age of onset for these malignancies should prompt closer physical examination of these sites by clinicians.
Six-Year Trends in Laboratory Computer Availability
Authors: Valenstein Paul , Walsh Molly
Published: January 2021

Context.—Failure of a clinical laboratory computer system can disrupt work flow and charge capture and affect patient care. The first comprehensive survey of computer downtime was conducted in 1995 and demonstrated significant interinstitutional variation in system availability. Despite numerous changes in the laboratory and computer industries since 1995, no follow-up study has been reported.

Objectives.—To quantify current laboratory computer availability and compare it with 1995 performance.

Design.—Ninety-seven laboratories prospectively recorded the frequency and duration of computer downtime during 30 days in 2001. Results were compared with 1995 survey data.

Results.—For the median facility, the number of downtime episodes decreased from 8 events per 30 days during 1995 to 3 events per 30 days during 2001 (P < .01). The frequency of unscheduled downtime also improved, from a median of 2 to 0.5 events per 30 days (P < .01). Reduced downtime events were paralleled by reduced cumulative downtime (14.3 vs 4.0 hours per 30 days; P < .01). Improvements were not restricted to the median facility; laboratories performing in the bottom quartile in 2001 recorded substantially less downtime than laboratories in the bottom quartile in 1995. When the comparison was restricted to the 37 institutions that participated in both the 1995 and 2001 surveys, a significant reduction in overall downtime and unscheduled downtime events was still evident (P < .01). More recent installation of vendor software patches was associated with a reduced frequency of downtime events in the 2001 data set.

Conclusion.—Laboratory computer downtime was less frequent in 2001 than in 1995; industry performance appears to be improving.
Amyloid A Gastrointestinal Amyloidosis Associated With Idiopathic Retroperitoneal Fibrosis
Authors: Hosaka Naoki , Ito Masaaki , Taki Yoji , Iwai Hiroshi , Toki Junko , Ikehara Susumu
Published: January 2021

We report a rare autopsy case of secondary gastrointestinal amyloid A (AA) amyloidosis associated with idiopathic retroperitoneal fibrosis (IRF) in a 67-year-old woman. Masses were identified around the aorta and inferior vena cava in her abdomen. Histologically, plasma cell infiltration was observed within fibrotic areas. Because no specific cause for the inflammatory mass was apparent, we diagnosed it as IRF. Steroid therapy, which usually reduces IRF masses, proved ineffective, and malabsorption syndrome developed 4 years later. On autopsy, amyloid protein was present systemically in the vascular walls of several organs, and deposition was highest in the gastrointestinal mucosa. Amyloid protein was identified as AA type, strongly suggesting that the amyloidosis was secondarily induced by IRF. To our knowledge, only 2 other cases of IRF-associated amyloidosis have been reported. Two of the 3 patients of these cases were women who showed resistance to steroid therapy.
Fibrosarcoma of the Ovary Arising in a Fibrothecomatous Tumor With Minor Sex Cord Elements
Authors: Lee Hwei-Yee , Ahmed Qasim
Published: January 2021

We report the case of a 69-year-old woman who presented with postmenopausal bleeding. Endometrial curettings showed complex atypical hyperplasia with focal well-differentiated adenocarcinoma. A computed tomographic scan of the abdomen revealed a right ovarian mass. Histologically, the right ovarian tumor was a fibrothecoma with minor sex cord elements showing focal fibrosarcomatous change. Fibrosarcoma of the ovary is a rare tumor that is considered to arise de novo or secondary to benign fibromatous tumors. Fibrothecoma of the ovary with minor sex cord elements is also a rare entity. To the best of our knowledge, this is the first reported case of a fibrosarcoma arising in a fibrothecoma with minor sex cord elements.