bluuebunny/crossref_metadata_2025 huggingface dataset:
An Evaluation of the Performance of Sysmex XE-2100 in Enumerating Nucleated Red Cells in Peripheral Blood
Authors: Gulati Gene , Behling Eric , Kocher William , Schwarting Roland
Published: February 2021

Context.—Automated methods of enumerating nucleated red blood cells (NRBCs) in blood are gaining acceptance in many laboratories.

Objective.—To evaluate the performance of Sysmex XE-2100 in enumerating NRBCs in peripheral blood.

Design.—Automated relative number of NRBCs per 100 white blood cells (NRBC%) results for a total of 460 specimens run on the XE-2100 were compared with manual NRBC% results obtained by performing a 100-cell differential on a Wright-stained smear prepared from each specimen. To assess within-day reproducibility, 64 specimens were rerun on the XE-2100, and a second 100-cell differential was performed on the original blood smear. Excel software was used for data analysis.

Results.—Regression analysis of automated NRBC% versus manual NRBC% yielded a correlation coefficient of 0.9712. No NRBCs were seen in the blood smear on 35 (15.1%) of 232 specimens with automated NRBC% of 0.1 to 1.9. The XE-2100 generated an NRBC% of 0.0 on 5 (6.8%) of 74 specimens, revealing 1 NRBC per 100 or more white blood cells by blood smear examination. The mean percent difference between duplicate automated results was 16.7 compared with 78.1 for the duplicate manual results. There were 9 instances in which the XE-2100 either did not detect the presence of more than 8 NRBCs per 100 white blood cells or generated an automated NRBC% of 18.1 or 18.8 when the smear revealed none. All of these were, however, flagged for smear review.

Conclusions.—Overall correlation between the automated and manual results was excellent. The automated method revealed better precision than the manual method. The number of specimens with false automated results was very small, and all were flagged for verification by a smear review.
Enterocolic Lymphocytic Phlebitis: Clinicopathologic Features and Review of the Literature
Authors: Ngo Nyethane , Chang Fuju
Published: February 2021

Enterocolic lymphocytic phlebitis (ELP) is a recently described entity and is of unknown etiology and pathogenesis. It is characterized by phlebitis of the bowel wall and mesentery, without arterial involvement or evidence of systemic vasculitis. The clinical presentation of ELP is varied, but it most commonly manifests with signs of an acute abdomen. Clinical, radiologic, and endoscopic findings are often conflicting and misdiagnosis is common as venous thrombosis is not suspected. The diagnosis of ELP is obtained histologically. There is a spectrum of histologic features associated with ELP, which includes lymphocytic phlebitis, necrotizing phlebitis, granulomatous phlebitis, and myointimal hyperplasia. Other features include venous thrombi and acute ischemic changes of the intestine. Surgical resection of the affected bowel is usually curative and recurrences are rare. The clinical and histopathologic features of ELP are reviewed.
p16 and Ki-67 Immunostaining in Atypical Immature Squamous Metaplasia of the Uterine Cervix: Correlation With Human Papillomavirus Detection
Authors: Iaconis Lori , Hyjek Elizabeth , Ellenson Lora H. , Pirog Edyta C.
Published: February 2021

Context.—Atypical immature squamous metaplasia (AIM) of the cervix is a loosely defined entity characterized by immature metaplastic cells with mild cytologic atypia.

Objective.—To examine whether a combination of immunostaining for p16 and Ki-67 could be used to stratify AIM cases into 3 categories: benign, cases with nondiagnostic atypia, and high-grade squamous intraepithelial lesion (HSIL).

Design.—The study consisted of 37 cases of AIM, 23 cases of benign cervical mucosa (NEG), and 36 cases of HSIL. All cases were tested for high-risk human papillomaviruses using SPF 10 polymerase chain reaction and immunostained for p16 and Ki-67.

Results.—All cases of HSIL were positive for both p16 and Ki-67. All but 2 benign control cases were negative for both p16 and Ki-67. Seven cases of AIM (19%) displayed a pattern of immunostaining identical to HSIL, and these most likely represent a spectrum of HSIL. A total of 54% of cases of AIM were negative for both p16 and Ki-67, consistent with benign reactive atypia. Two AIM cases (5%) were negative for p16 and positive for Ki-67 in the area adjacent to an ulcer, representing regeneration. Finally, 22% of AIM cases were positive for p16 and negative for Ki-67; such cases may represent a precursor of HSIL or, alternatively, a regressing HSIL.

Conclusion.—The combination of immunostaining for p16 and Ki-67 is helpful in limiting of the number of cases with nondiagnostic atypia of the cervix.
Expression of Activated and Latent Signal Transducer and Activator of Transcription 3 in 303 Non–Small Cell Lung Carcinomas and 44 Malignant Mesotheliomas: Possible Role for Chemotherapeutic Intervention
Authors: Achcar Rosanede Oliveira Duarte , Cagle Philip T. , Jagirdar Jaishree
Published: February 2021

Context.—Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse human cancers and plays a critical role in tumor cell survival, proliferation, migration, invasion, angiogenesis, and inhibition of apoptosis. The phosphorylated active form of STAT3 (pSTAT3) mediates its effects via nuclear transcriptional activity. However, it was recently observed that the nonphosphorylated, cytoplasmic, inactive form of STAT3 is involved in cell motility and consequently tumor invasion. It appears that, although STAT3 is not absolutely required for tumor formation, tumors that develop in the presence of STAT3 become dependent on its expression for their survival, making it a potential therapeutic target.

Objective.—To investigate the possible utility of STAT3 as a future therapeutic target in non–small cell lung carcinoma (NSCLC) and malignant mesothelioma (MM).

Design.—Immunohistochemical expression of MIB-1, STAT3, and pSTAT3 was assessed in 303 NSCLC and 44 MM archival cases.

Results.—A more conspicuous expression of inactive STAT3 (91.44% in NSCLC and 79.5% in MM cases) was present compared with the nuclear activated form pSTAT3 (60.53% in NSCLC and 61.4% in MM cases). MIB-1 did not correlate with the expression of STAT3 or pSTAT3.

Conclusions.—The strong expression of cytoplasmic inactive STAT3 in NSCLC and MM cases implies a major role for STAT3 in tumor motility, invasion, and metastasis via a nontranscriptional pathway. We conclude that STAT3 and pSTAT3 are up-regulated in a high percentage of NSCLCs and MMs, regardless of tumor type, age, sex, smoking status, stage and grade of tumor, or survival, providing a basis for therapeutic intervention.
Glial Fibrillary Acidic Protein and CD57 Immunolocalization in Cell Block Preparations Is a Useful Adjunct in the Diagnosis of Pleomorphic Adenoma
Authors: Shah Sejal S. , Chandan Vishal S. , Wilbur David C. , Khurana Kamal K.
Published: February 2021

Context.—The cytologic distinction between pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) can be diagnostically challenging in aspirate smears. Hence a cytologic diagnosis of “atypical cytology” with a differential diagnosis including PA and ACC is occasionally rendered in a subset of salivary gland fine-needle aspirations.

Objective.—To evaluate the role of glial fibrillary acidic protein (GFAP) and CD57 expression in cell block material obtained during fine-needle aspiration procedure in differentiating PA from ACC.

Design.—We performed GFAP and CD57 immunostains on formalin-fixed, paraffin-embedded cell block sections of 26 salivary gland fine-needle aspiration cases with the following cytologic diagnoses: (1) PA (10 cases); (2) atypical cytology, cannot exclude ACC (8 cases); and (3) ACC (8 cases).

Results.—All 10 (100%) cases with cytologic diagnoses of PA were positive for GFAP, and 8 (80%) of 10 cases were positive for CD57; tissue follow-up confirmed the diagnosis of PA in all cases. All 8 (100%) cases with cytologic diagnosis of ACC were negative for both GFAP and CD57; tissue follow-up confirmed the diagnoses of ACC in all cases. Of the 8 cases with diagnoses of atypical cytology, 4 (50%) were negative and 4 (50%) were positive for both GFAP and CD57. Subsequent tissue follow-up in these cases revealed 4 cases of ACC (all negative for GFAP and CD57) and 4 cases of PA (all positive for GFAP and CD57).

Conclusions.—Our results show that positive staining for GFAP and CD57 serves as a useful adjunct for the diagnosis of PA and helps to reduce the uncertainty in challenging cases.
Intraneural Perineurioma: A Systematic Review With Illustrative Cases
Authors: Boyanton Jr. Bobby L. , Jones John K. , Shenaq Saleh M. , Hicks M. John , Bhattacharjee Meenakshi B.
Published: February 2021

Context.—Intraneural perineurioma may be confused with other “onion bulb” Schwann cell entities (localized hypertrophic neuropathy, reactive/demyelinating processes, or inherited polyneuropathies of Charcot-Marie-Tooth/Dejerine Sottas) due to similar clinical, radiologic, and histologic features. Perineurial and Schwann cells can only be differentiated by ultrastructure and immunohistochemsitry.

Objective.—To identify and summarize the clinicopathologic features of true cases of intraneural perineurioma from the English language literature.

Data Sources.—A systematic review was performed on definitive intraneural perineuriomas identified through Medline. Baylor College of Medicine–affiliated hospitals' anatomic pathology databases yielded 2 illustrative intraneural perineurioma cases.

Study Selection.—Intraneural perineurioma inclusion criteria consisted of characteristic histology and confirmation of perineurial cell lineage by either immunohistochemistry (epithelial membrane antigen positive, S100 protein negative) and/or ultrastructural analysis (thin cytoplasmic processes with an incomplete basal lamina, poorly formed tight junctions, and pinocytotic vesicles).

Data Extraction.—Clinicopathologic data were extracted from all identified articles, with subsequent statistical analysis of the following parameters: age, sex, race, tumor location, tumor size, duration of symptoms prior to diagnosis, treatment modalities and outcomes measures, follow-up assessment for tumor recurrence and metastasis, clinical features (history of trauma, motor/sensory abnormalities, clinical/family history), and diagnostic workup (routine histology, immunohistochemistry, ultrastructural analysis, and molecular/cytogenetic characteristics).

Conclusions.—Intraneural perineurioma is a neoplastic proliferation of perineurial cells with unique immunohistochemistry and ultrastructural features, and it is distinct from other onion bulb Schwann cell–derived entities. Despite harboring molecular abnormalities of the long arm of chromosome 22, intraneural perineurioma has not been associated with neurofibromatosis. Intraneural perineurioma is a benign peripheral nerve sheath tumor that does not recur or metastasize.
Breast Carcinoma Arising in Microglandular Adenosis: A Review of the Literature
Authors: Salarieh Afshin , Sneige Nour
Published: February 2021

Microglandular adenosis is widely known as a benign breast lesion that can produce a mass. It differs from other types of adenosis by having an infiltrative pattern of growth and glands lacking a myoepithelial layer. Although in every other aspect the cells lining the glands are epithelial, they stain strongly with S100 protein. Most cases of microglandular adenosis are resolved after adequate excision, but more recent data suggest that this lesion may be a precursor for carcinoma, with atypical microglandular adenosis being an intermediate lesion. Carcinomas arising in a background of microglandular adenosis, although they may be low grade, are commonly estrogen and progesterone receptor negative, in contrast to most conventional low-grade carcinomas unrelated to microglandular adenosis. They also show immunopositivity for S100 protein, similar to microglandular adenosis. Diagnostic problems include differentiating microglandular adenosis from carcinoma and assessing the extent of the carcinoma component. In this review, we discuss the histomorphologic and immunophenotypic characteristic of the spectrum of microglandular adenosis lesions with emphasis on diagnostic features distinguishing microglandular adenosis from well-differentiated carcinoma, in particular, tubular carcinoma, and assessment of surgical margins of excision in such lesions.
Mixed Glioneuronal Tumors: Recently Described Entities
Authors: Edgar Mark A. , Rosenblum Marc K.
Published: February 2021

Context.—Several distinctive mixed glioneuronal tumors that warrant recognition as clinicopathologic entities have been recently described by neuropathologists.

Objective.—To summarize important clinical, radiologic, and pathologic findings for 3 novel glioneuronal tumors (papillary glioneuronal tumor, rosetted glioneuronal tumor, and rosette-forming glioneuronal tumor of the fourth ventricle).

Data Sources.—Recent reports in the pathology literature and the authors' experience with mixed glioneuronal tumors at a major cancer center.

Conclusions.—Histologic features enabling recognition of these recently described glioneuronal tumors are presented along with remarks concerning the classification of mixed neuronal and glial tumors exhibiting unconventional appearances.
Relevance of the Autopsy as a Medical Tool: A Large Database of Physician Attitudes
Authors: Hooper Jody E. , Geller Stephen A.
Published: February 2021

Context.—Autopsy rates for patients dying in hospitals have declined from approximately 50% in the 1950s to 5% or less today.

Objective.—To investigate the nature of physician attitudes about autopsy in a large and varied population and to relate these attitudes to certain physician demographic variables.

Design.—A 10-question, anonymous, multiple-choice format questionnaire was distributed to all attending physicians at 4 hospitals: 2 that were university-affiliated (1 private and 1 public), 1 military, and 1 private nonuniversity-affiliated medical center. A total of 2608 surveys were distributed.

Results.—Three hundred eighty-eight (15%) physicians responded to the survey. Respondents agreed (77%) that autopsy results could affect their future medical practice, and disagreed (73%) that the accuracy of modern diagnostic procedures makes autopsy unnecessary. Most respondents (72%) disagreed that litigation concerns play a role in the decision to request autopsy. Spearman correlation coefficients found 9 significant relationships among the survey items, with many correlations reflecting statistically significant relationships between demographic and attitudinal variables.

Conclusions.—The survey data and statistical analysis confirm that respondents value the autopsy as a relevant clinical tool, in spite of declining requests. One of the most crucial factors influencing attitudes is the physician's level of experience with autopsy in training and practice. Among other interesting results was that strength of belief in autopsy relevancy correlates significantly (P = .003) with greater prior exposure to the autopsy. In a sense, the current low autopsy rates may be self-perpetuating because of the paucity of and decreasing experience with autopsy by succeeding generations of clinicians.
The Endometrium
Authors: Silverberg Steven G.
Published: February 2021

Context.—Endometrial tissue specimens are commonly encountered in daily practice. It is well known that a number of problematic diagnostic scenarios occur relative to these specimens.

Objective.—To emphasize practical aspects of endometrial specimen handling and reporting, with selected comments on common diagnostic pitfalls, including (1) the diagnosis of endometrial intraepithelial carcinoma in atrophic endometrial biopsy specimens, (2) evaluation of adequacy of endometrial sampling specimens, (3) problems in diagnosing and measuring the depth of myometrial invasion in endometrial carcinoma, (4) the question of metastasis versus independent primaries in concurrent carcinomas of endometrium and one or both ovaries, (5) the problematic differential diagnoses between type 1 (primarily endometrioid) and type 2 (primarily serous) adenocarcinomas, and (6) atypical hyperplasia and proposed classification systems for its replacement.

Data Sources.—Published literature, consensus statements, and personal experience.

Conclusions.—A systematic approach to the handling and reporting of endometrial specimens reduces the potential for omission and error. Recognition of diagnostic pitfalls and practical approaches to their resolution help improve quality.
Glioblastoma
Authors: Miller C. Ryan , Perry Arie
Published: February 2021

Context.—Glioblastoma (GBM), the most common primary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3 distinct morphologic variants of GBM are currently recognized by the current World Health Organization classification scheme, including GBM, giant cell GBM, and gliosarcoma. Additional variants, some of which have significant morphologic overlap with tumors that have more favorable prognosis and treatment response rates, particularly anaplastic oligodendroglioma, have been described since its publication in 2000 and may be included in the next classification.

Objective.—To summarize the morphologic and molecular genetic diversity of both well-established and novel GBM variants and outline our approach to these heterogeneous neoplasms and their distinction from other diffuse, high-grade gliomas.

Data Sources.—Published literature and our own experience in an active academic diagnostic surgical neuropathology practice were reviewed.

Conclusions.—Precise subclassification of GBM is required for accurate prognostication and appropriate treatment planning.
Recurring Translocation (10;17) and Deletion (14q) in Clear Cell Sarcoma of the Kidney
Authors: Brownlee Noel A. , Perkins L. Allen , Stewart Will , Jackle Beth , Pettenati Mark J. , Koty Patrick P. , Iskandar Samy S. , Garvin A. Julian
Published: February 2021

Context.—Clear cell sarcoma of the kidney (CCSK) is a prognostically unfavorable renal neoplasm of childhood. Previous cytogenetic studies of CCSK have reported balanced translocations t(10;17)(q22;p13) and t(10;17)(q11; p12). Although the tumor suppressor gene p53 is located at the chromosome 17p13 breakpoint, p53 abnormalities are rarely present in these tumors.

Objective.—To identify cytogenetic abnormalities in CCSK and correlate these findings with other clinicopathologic parameters.

Design.—A retrospective review of CCSK patients from 1990 to 2005 was conducted at our medical center. We performed clinical and histologic review, p53 immunohistochemical and classic cytogenetics (or ploidy analysis), and p53 fluorescence in situ hybridization analyses.

Results.—Five male patients (age range, 6 months to 4 years) were identified with cytogenetic abnormalities. Of 3 cytogenetically informative cases, one revealed a clonal balanced translocation t(10;17)(q22;p13) and an interstitial deletion of chromosome 14, del(14)(q24.1q31.1), and the other 2 patients had normal karyotypes. Fluorescence in situ hybridization for p53 in the t(10;17) case revealed no deletion. Immunohistochemical evaluation of p53 demonstrated lack of nuclear protein accumulation in all cases.

Conclusions.—Together with the published literature, our results indicate that translocation (10;17) and interstitial deletions of chromosome 14q are recurring cytogenetic lesions in CCSK. To date, 3 cases of CCSK or “sarcomatoid Wilms tumors” have been reported to exhibit t(10;17). One previously reported case of CCSK contained deletion 14q. Results of p53 immunohistochemistry and/or p53 fluorescence in situ hybridization in this report suggest lack of mutations or deletions of this tumor suppressor in these CCSK cases. The t(10;17) breakpoint and deletion of chromosome 14q24 suggest that other genes are involved in tumor pathogenesis.
The Role of Periadventitial Fat in Atherosclerosis
Authors: Vela Deborah , Buja L. Maximilian , Madjid Mohammad , Burke Alan , Naghavi Morteza , Willerson James T. , Casscells S. Ward , Litovsky Silvio
Published: February 2021

Context.—It has become increasingly evident that adipose tissue is a multifunctional organ that produces and secretes multiple paracrine and endocrine factors. Research into obesity, insulin resistance, and diabetes has identified a proinflammatory state associated with obesity. Substantial differences between subcutaneous and omental fat have been noted, including the fact that omental fat produces relatively more inflammatory cytokines. Periadventitial fat, as a specific adipose tissue subset, has been overlooked in the field of atherosclerosis despite its potential diagnostic and therapeutic implications.

Objective.—To review (1) evidence for the role of adventitial and periadventitial fat in vessel remodeling after injury, (2) the relationship between adventitial inflammation and atherosclerosis, (3) the association between periadventitial fat and plaque inflammation, and (4) the diagnostic and therapeutic implications of these roles and relationships for the progression of atherosclerosis.

Data Sources.—We present new data showing greater uptake of iron, administered in the form of superparamagnetic iron oxide, in the periadventitial fat of atherosclerotic mice than in control mice. In addition, macrophage density in the periadventitial fat of lipid-rich plaques is increased compared with fibrocalcific plaques.

Conclusions.—There is a striking paucity of data on the relationship between the periadventitial fat of coronary arteries and atherosclerosis. Greater insight into this relationship might be instrumental in making strides into the pathophysiology, diagnosis, and treatment of coronary artery disease.
Double Immunohistochemical Staining With MUC4/p53 Is Useful in the Distinction of Pancreatic Adenocarcinoma From Chronic Pancreatitis: A Tissue Microarray-Based Study
Authors: Bhardwaj Atul , Marsh, Jr William L. , Nash Jason W. , Barbacioru Catalin C. , Jones Susie , Frankel Wendy L.
Published: February 2021

Context.—Immunohistochemical stains have been used for the distinction of pancreatic adenocarcinoma from chronic pancreatitis.

Objective.—To determine if a double stain for MUC/p53 improved specificity and sensitivity for distinction of pancreatic andenocarcinoma from chronic pancreatitis by comparing maspin, mucin 4 (MUC4), p53, Smad4, and the double stain MUC4/p53.

Design.—Seventy-four pancreatic adenocarcinomas and 19 chronic pancreatitis cases were retrieved from archival files. Tissue cores were arrayed to create a tissue microarray of 2-mm cores. Sections were stained with antibodies against maspin, MUC4, p53, and Smad4. Additionally, a 2-color, double stain for MUC4 and p53 was developed and evaluated. Five percent or greater staining in either of the cores was considered positive. Intensity (0, 1, 2) and extent (%) of tumor cells staining was also determined.

Results.—The sensitivity for distinction of pancreatic adenocarcinoma from chronic pancreatitis with maspin, MUC4, p53, and Smad4 was 90%, 77%, 60%, and 63%, respectively; the specificity was 67%, 78%, 88%, and 88%, respectively. When MUC4 and p53 were combined in a double stain, and positive staining for either considered a positive result, the sensitivity increased to 96% but specificity was 73%. When immunoreactivity for both antibodies was necessary for a positive result, sensitivity fell to 39% but specificity was 100%. No correlation was found between intensity or extent of staining with any of the individual stains and tumor differentiation.

Conclusion.—The double immunohistochemical stain for MUC4/p53 can be a useful diagnostic tool in conjunction with the hematoxylin-eosin–stained section for pancreatic adenocarcinoma, particularly when limited tumor is available for multiple stains.
Questionable Role of Human Herpesviruses in the Pathogenesis of Kikuchi Disease
Authors: Cho Min-Sun , Choi Hee Jung , Park Hae Kyung , Cho Sung Eun , Han Woon Sup , Yang Woo Ick
Published: February 2021

Context.—Kikuchi disease is a self-limiting febrile lymphadenopathy characterized by a patchy area of apoptosis. Kikuchi disease is thought to be caused by a virus, but this has not been clearly demonstrated. Human herpesviruses 6 and 7 (HHV-6 and HHV-7) are lymphotropic viruses that can induce apoptosis in infected lymphocytes. Recently, HHV-8 was reported to be a possible etiologic agent of Kikuchi disease.

Objective.—To investigate the incidence of HHV-6, HHV-7, and HHV-8 infection in patients with Kikuchi disease.

Design.—Seventy archival tissue specimens (from 50 Kikuchi disease cases and 20 control cases) were tested for the presence of HHV-6 and HHV-7 using a nested polymerase chain reaction, and for the presence of HHV-8 using single-step polymerase chain reaction. Immunohistochemistry for HHV-8 expression was carried out in those cases in which HHV-8 was detected using polymerase chain reaction.

Results.—Of the 50 cases with Kikuchi disease, 21 (42%) were HHV-6 positive and 32 (64%) were HHV-7 positive. Eight (40%) of the 20 control cases were HHV-6 positive and 9 (45%) were HHV-7 positive. Both HHV-6 and HHV-7 were detected in 15 (30%) of the cases with Kikuchi disease and in 3 (15%) of the control cases. Three (6%) of the 50 cases of Kikuchi disease were HHV-8 positive but revealed no positive cells on immunohistochemical analysis for HHV-8. Human herpesvirus 8 was not expressed in any of the control cases.

Conclusions.—There was no association between the presence of HHV-6 or HHV-7 and Kikuchi disease. Because the HHV-8 genome but not protein was detected in a small proportion of the cases of Kikuchi disease, its potential causative role in this disease should be determined by further studies.
Significance of Margin and Extent of Dysplasia in Loop Electrosurgery Excision Procedure Biopsies Performed for High-Grade Squamous Intraepithelial Lesion in Predicting Persistent Disease
Authors: Tyler Lisa N. , Andrews Nancy , Parrish Rudolph S. , Hazlett Linda J. , Korourian Soheila
Published: February 2021

Context.—High-grade squamous intraepithelial lesions (cervical intraepithelial neoplasia 2 and 3) are commonly treated with loop electrosurgery excision procedure (LEEP) biopsies.

Objective.—To highlight the significance of positive margins and extent of positive margins of the cervical LEEP biopsies in predicting the persistence of high-grade squamous intraepithelial lesion and to provide suggestions for reporting margins in cervical LEEP biopsies.

Design.—The pathology files at the University of Arkansas for Medical Sciences were searched for cervical intraepithelial neoplasia 2 and 3 treated by LEEP biopsy from 1990 to 2001.

Results.—A total of 489 LEEP biopsy specimens were retrieved and reviewed; 270 patients had follow-up within 1 year. The biopsy specimens of 110 patients showed positive endocervical margins. One hundred sixty specimens had negative ectocervical-endocervical margins. Follow-up of 54% of the cases with initial positive margins showed residual high-grade squamous intraepithelial lesions. This association was even greater when multiple blocks showed positive endocervical margins and in cases with positive deep margins. On the other hand, a negative margin predicted ability to completely remove the lesion in 95% of patients.

Conclusion.—This study reiterates the significance of the evaluation of the margin, even in samples that were received as multiple fragments. Reporting of LEEP biopsy findings should include the extent of the dysplasia, the status of the ectocervical-endocervical margin, and the status of the deep margin.
Adenoid Cystic/Basal Cell Carcinoma of the Prostate: Review and Update
Authors: Begnami Maria Dirlei , Quezado Martha , Pinto Peter , Linehan W. Marston , Merino Maria
Published: February 2021

Context.—Although most prostate carcinomas are of the conventional acinar type, unusual variants have been reported. Adenoid cystic/basal cell carcinoma of the prostate is a rare tumor with distinctive histopathologic features. There are only a few publications in the literature concerning the diagnosis, treatment, and prognosis of this neoplasm.

Objective.—To review current literature together with the clinical, pathologic, and immunohistochemical features of adenoid cystic/basal cell carcinoma of the prostate and offer a practical approach to the diagnosis—including the differential diagnosis—of this neoplasm in surgical pathologic specimens.

Data Sources.—Adenoid cystic/basal cell carcinoma of the prostate is composed of infiltrating basaloid cells forming dilated acinar and cribriform spaces with luminal basementlike material. Differentiation of adenoid cystic/basal cell carcinoma from basal cell hyperplasia and cribriform pattern of acinar adenocarcinoma may be difficult. The use of cytokeratin 34βE12 and prostate-specific antigen can help in difficult cases. Most cases are indolent, but metastasis has been documented in a few cases.

Conclusions.—Various histologic and immunohistochemical features are helpful in recognizing adenoid cystic/basal cell carcinoma of the prostate. This is a rare subtype of prostate cancer and correct diagnosis is important because of the unique clinical and biological features and the implications for treatment and prognosis.
Epithelial Marker–Negative Desmoplastic Small Round Cell Tumor With Atypical Morphology: Definitive Classification by Fluorescence In Situ Hybridization
Authors: Zhang Jie , Dalton James , Fuller Christine
Published: February 2021

Desmoplastic small round cell tumor typically presents with abundant desmoplastic stroma containing nested primitive round cells bearing a polyphenotypic immunohistochemical profile. Lesions with minimal classic morphology pose a formidable diagnostic challenge. The current case represents one such example, arising as a large abdominal-pelvic mass in a 17-year-old female patient. The tumor was composed of a monomorphous population of small round cells lining microcystic structures and forming pseudoacini and fine anastomosing trabeculae and cords. The stroma was abundantly myxoid with only occasional thick desmoplastic septa. The tumor cells were variably immunopositive for vimentin, desmin, smooth muscle actin, synaptophysin, neuron-specific enolase, Bcl-2 and WT1 (nuclear); epithelial markers were negative. The definitive diagnosis of desmoplastic small round cell tumor was rendered with the demonstration of the characteristic EWS-WT1 gene fusion by fluorescence in situ hybridization. The current case emphasizes the utility of fluorescence in situ hybridization to demonstrate EWS-WT1 gene fusion in desmoplastic small round cell tumor with nonclassic morphologic and immunohistochemical features to avoid potential misdiagnosis.
Kimura Disease
Authors: Abuel-Haija Mohammad , Hurford Matthew T.
Published: February 2021

Kimura disease is a benign rare chronic inflammatory disorder of unknown etiology that involves the lymph nodes and subcutaneous tissue of the head and neck regions. Elevated serum immunoglobulin E levels and peripheral blood eosinophilia are also common. This disease is most common in middle-aged Asian men. Although the etiology is unknown, it most probably represents an aberrant chronic immune response. Treatment for Kimura disease includes surgical resection and regional or systemic steroid therapy. Cytotoxic therapy and radiation have also been utilized. The disease has an excellent prognosis, although it may recur locally.
Oxygen Therapeutics: Pursuit of an Alternative to the Donor Red Blood Cell
Authors: Ness Paul M. , Cushing Melissa M.
Published: February 2021

Context.—There is no true substitute for the many functions of human red blood cells, and synthetic products will not replace the need for blood donation in the foreseeable future. Hemoglobin-based oxygen carriers have many characteristics that would serve as a useful adjunct to red cells in clinical settings. Over time, these technologies have the potential to dramatically reshape the practice of transfusion medicine.

Objective.—To review the characteristics and potential utility of hemoglobin-based oxygen carriers and perfluorocarbon-based oxygen carriers. Several hemoglobin-based oxygen carriers are under study in phase III clinical trials. Novel uses for synthetic oxygen therapeutics are emphasized.

Data Sources.—All published reports with the key words oxygen therapeutics, blood substitutes, and red cell substitutes from 1933 until March 2006 were searched through Medline. Significant findings were synthesized.

Conclusions.—Recognition of the true impact of red cell substitutes is still several years away. The most compelling products, hemoglobin-based oxygen carriers, have potential use in trauma, providing immediate oxygen-carrying support in the face of alloantibodies or autoantibodies, and in other clinical situations in which long-term survival of red cells is not essential. In the interim, efforts should be focused on enhancing the current blood supply system while supporting ongoing and planned blood substitute research efforts, including trials assessing novel clinical indications for these products.
Systemic Mastocytosis: A Concise Clinical and Laboratory Review
Authors: Patnaik Mrinal M. , Rindos Michelle , Kouides Peter A. , Tefferi Ayalew , Pardanani Animesh
Published: February 2021

Context.—Systemic mastocytosis is characterized by abnormal growth and accumulation of neoplastic mast cells in various organs. The clinical presentation is varied and may include skin rash, symptoms related to release of mast cell mediators, and/or organopathy from involvement of bone, liver, spleen, bowel, or bone marrow.

Objective.—To concisely review pathogenesis, disease classification, clinical features, diagnosis, and treatment of mast cell disorders.

Data Sources.—Pertinent literature emerging during the last 20 years in the field of mast cell disorders.

Conclusions.—The cornerstone of diagnosis is careful bone marrow histologic examination with appropriate immunohistochemical studies. Ancillary tests such as mast cell immunophenotyping, cytogenetic/molecular studies, and serum tryptase levels assist in confirming the diagnosis. Patients with cutaneous disease or with low systemic mast cell burden are generally managed symptomatically. In the patients requiring mast cell cytoreductive therapy, treatment decisions are increasingly being guided by results of molecular studies. Most patients carry the kit D816V mutation and are predicted to be resistant to imatinib mesylate (Gleevec) therapy. In contrast, patients carrying the FIP1L1-PDGFRA mutation achieve complete responses with low-dose imatinib therapy. Other therapeutic options include use of interferon-α, chemotherapy (2-chlorodeoxyadenosine), or novel small molecule tyrosine kinase inhibitors currently in clinical trials.
Hypercoagulation Testing in Ischemic Stroke
Authors: Rahemtullah Aliyah , Van Cott Elizabeth M.
Published: February 2021

Context.—The utility of laboratory testing for hypercoagulability in the setting of stroke is uncertain.

Objective.—To review the current literature and to make recommendations with regard to laboratory testing for various hypercoagulability risk factors for ischemic stroke.

Data Sources.—Published articles studying the utility of various hypercoagulation tests in predicting initial and/or recurrent stroke or transient ischemic attack as well as cerebral vein thrombosis were collected and reviewed, with an emphasis on prospective studies.

Conclusions.—Certain tests, such as C-reactive protein, homocysteine, antiphospholipid antibodies, and lipoprotein(a), may be useful in patients with a history of stroke or at high risk for stroke, as evidenced by prospective data. Factor V Leiden, prothrombin G20210A, protein C, protein S, and antithrombin are not recommended for routine testing but may be useful in certain populations, such as in pediatric patients or in patients with cerebral vein thrombosis.
Transfusion of Platelets Containing ABO-Incompatible Plasma: A Survey of 3156 North American Laboratories
Authors: Fung Mark K. , Downes Katharine A. , Shulman Ira A.
Published: February 2021

Context.—Hemolytic transfusion reactions due to platelet transfusions containing ABO-incompatible plasma (ie, group O platelets into a non–group O patient) have been reported in the literature. However, limited data describe the extent to which transfusion services manage such platelet transfusions or the methods used to limit the risk of such reactions.

Objective.—To determine transfusion services' current practices regarding the use of platelets containing ABO-incompatible plasma.

Design.—In a College of American Pathologists' Transfusion Medicine Proficiency Testing Survey, supplemental questions asked participants whether a policy existed for the use of platelets containing ABO-incompatible plasma and, if a policy existed, what elements were part of the policy.

Results.—Of 3156 laboratories that transfused platelets, 3152 responded to the question of whether they had a policy. Of these respondents, 83% (n = 2623) had a policy. One or more elements were reported for transfusions in adults: only ABO-compatible plasma products (n = 1363); only ABO-compatible plasma and platelet products (n = 679); notification of medical director (n = 646); notification of ordering physician (n = 637); volume limit of ABO-incompatible plasma allowed (n = 255); volume-reduction of ABO-incompatible products (n = 168); screening for critical titer of anti-A or anti-B (n = 53). A total of 529 laboratories indicated that they did not have a policy.

Conclusions.—A majority of laboratories have a policy, but most do not include a method to limit the risk of hemolysis if platelets containing ABO-incompatible plasma must be transfused. When such platelets are used, there does not appear to be consensus on a specific method to minimize the transfusion of anti-A or anti-B.
Quantitation of Plasma Cells in Bone Marrow Aspirates by Flow Cytometric Analysis Compared With Morphologic Assessment
Authors: Smock Kristi J. , Perkins Sherrie L. , Bahler David W.
Published: February 2021

Context.—Accurate quantitation of bone marrow plasma cells is an important component in the diagnosis and posttreatment assessment of plasma cell dyscrasias. Although flow cytometry is sometimes used for this purpose and can rapidly evaluate many cells, the accuracy of flow-based plasma cell quantitation compared with morphologic assessment (currently the gold standard) is uncertain as direct comparison studies have not been previously reported.

Objective.—To determine how percentages of plasma cells in diagnostic aspirate smears quantitated by morphologic assessment relate to percentages of plasma cells quantified by flow cytometry.

Design.—Thirty bone marrow cases with 10% or more plasma cells and leukemia/lymphoma flow cytometry immunophenotyping studies were identified from our hematopathology database. The Wright-stained aspirate smears, marrow biopsy sections, and flow cytometry histograms were reviewed.

Results.—Morphologically determined plasma cell percentages from the diagnostic aspirate smears were consistently higher than those determined by flow cytometry. Much of this difference appeared to be related to differences in sample quality. However, the cellular processing involved in performing flow cytometry also appeared to reduce plasma cell percentages in many cases.

Conclusions.—This study helps define the limitations of flow cytometry for quantitating plasma cell loads in marrow aspirate specimens that may significantly affect the diagnosis or assessment of treatment response.
Splenic Metastases: Clinicopathologic Presentation, Differential Diagnosis, and Pathogenesis
Authors: Compérat Eva , Bardier-Dupas Armelle , Camparo Philippe , Capron Frédérique , Charlotte Frédéric
Published: February 2021

Context.—Splenic metastases from solid tumors, defined as parenchymal lesion, are considered exceptional. Nevertheless, the number of case reports has been increasing due to the improvement of imaging techniques and the long-term follow-up of patients with cancer. Splenic metastases occur in a context of multivisceral disseminated cancer or as a solitary lesion.

Objective.—To provide a general overview of the clinicopathologic features, differential diagnosis, and pathogenesis of splenic metastases.

Data Sources.—Relevant articles indexed in PubMed (National Library of Medicine) database. The search was based on the following terms: (metastasis or metastases) and spleen.

Conclusions.—The most common primary sources of splenic metastasis are breast, lung, colorectal, and ovarian carcinomas and melanoma in cases of multivisceral cancer and colorectal and ovarian carcinomas in cases of solitary splenic lesion. Splenectomy can be replaced by less aggressive methods such as fine-needle aspiration or percutaneous biopsy for establishing the diagnosis of solitary splenic metastasis. The main differential diagnoses are primary lymphoma, vascular tumors, and infectious lesions of the spleen. The relative rarity of splenic metastases could be explained by anatomic factors and the inhibitory effect of the splenic microenvironment on the growth of metastatic cells. The analysis of clinical case reports suggests that solitary splenic metastases may result from the growth of an early blood-borne micrometastasis following a period of clinical latency, often several years after the diagnosis of the primary tumor.
Hansen Disease in the United States in the 21st Century: A Review of the Literature
Authors: Anderson Heather , Stryjewska Barbara , Boyanton Bobby L. , Schwartz Mary R.
Published: February 2021

In this article we review the recent literature on Hansen disease (leprosy). We searched published literature through PubMed (National Library of Medicine) and extracted data through direct review of the literature and pathologic slides. Hansen disease continues to occur in the United States, including among the native-born population. Inclusion of the disease in the differential diagnosis is key to confirmation. Current epidemiology, classification systems, prevention measures, and therapy are reviewed.
Solid Organ Transplant-Associated Acute Graft-Versus-Host Disease
Authors: Zhang Yaxia , Ruiz Phillip
Published: February 2021

Solid organ transplant–associated graft-versus-host disease is an infrequent and potentially lethal complication. The incidence of this complication varies according to the type of organ transplant with higher rates associated with liver and small bowel transplants. The clinical presentation typically includes fever and skin rash, and most cases quickly advance to become a multisystem disease affecting the bone marrow and other nontransplanted solid organs. The diagnosis is based on the clinical symptoms, pathologic changes in biopsied tissues, and systemic lymphoid chimerism. The mortality of this disease can exceed 75% after liver transplant and most patients die from infections or hemorrhage due to bone marrow failure. There is no standard treatment strategy for this complication, and the management mainly consists of both prophylaxis and immediate treatment without delay. This short review summarizes the current pathogenesis, diagnosis, and treatment of this entity.
Pseudoangiomatous Stromal Hyperplasia: An Overview
Authors: Virk Renu K. , Khan Ashraf
Published: February 2021

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign, proliferative mesenchymal lesion with possible hormonal etiology. It typically affects women in the reproductive age group. Pseudoangiomatous stromal hyperplasia is frequently an incidental histologic finding in breast biopsies performed for other benign or malignant lesions. Rarely, it can present as a firm, painless breast mass, which has been referred to as nodular or tumorous PASH. Grossly, tumorous PASH is a well-circumscribed, firm, rubbery mass with solid, homogenous, gray-white cut surface. On histologic examination, it is characterized by the presence of open slitlike spaces in dense collagenous stroma. The spaces are lined by a discontinuous layer of flat, spindle-shaped myofibroblasts with bland nuclei. The spindle cells express progesterone receptors and are positive for vimentin, actin, and CD34. The most important differential diagnosis on histopathology is angiosarcoma. Pseudoangiomatous stromal hyperplasia discovered incidentally does not require any additional specific treatment. Tumorous PASH is treated by local surgical excision with clear margins and the prognosis is excellent, with minimal risk of recurrence after adequate surgical excision.
Lung Tumors With Neuroendocrine Morphology: Essential Radiologic and Pathologic Features
Authors: Franks Teri J. , Galvin Jeffrey R.
Published: February 2021

Context.—Tumors with neuroendocrine morphology are a distinct subset of lung neoplasms sharing characteristic histologic, immunohistochemical, ultrastructural, and molecular features.

Objective.—To review the current histologic classification and the diagnostic criteria for the major categories of neuroendocrine tumors of the lung.

Data Sources.—Published classification systems from the World Health Organization and pertinent peer-reviewed articles indexed in PubMed (National Library of Medicine) form the basis of this review.

Conclusions.—Accurate classification of the neuroendocrine tumors of the lung requires knowledge of specific criteria separating the major categories, which is essential for determining prognosis and treatment.
Immunohistochemistry of Pulmonary and Pleural Neoplasia
Authors: Beasley Mary Beth
Published: February 2021

Context.—The use of immunohistochemical stains has several applications in the evaluation of pulmonary and pleural neoplasms. The number of available immunohistochemical stains is continually expanding and, although these stains are an important diagnostic adjunct, their use is not without limitations and pitfalls.

Objective.—To review and summarize the primary immunohistochemical applications with regard to the most common pulmonary and pleural neoplasms and discuss newly developed markers and common pitfalls.

Data Sources.—Pertinent peer-reviewed literature emphasizing immunohistochemical applications in common lung and pleural tumors, unusual and problematic staining patterns in frequently encountered subtypes/histologic variants, and recently developed immunohistochemical stains of potential promise.

Conclusions.—Immunohistochemical stains provide the greatest aid in establishing the site of origin of adenocarcinomas encountered in the lung and in separating epithelioid mesothelioma from adenocarcinoma. Certain subtypes of pulmonary adenocarcinomas may exhibit unusual staining patterns that may be potentially problematic. Immunohistochemistry has a more limited role in separating small cell carcinoma from non–small cell carcinoma, and extreme caution must be used in the situation of crushed biopsy specimens.