bluuebunny/crossref_metadata_2025 huggingface dataset:
True Malignant Mixed Tumor (Carcinosarcoma) of Parotid Gland With Unusual Mesenchymal Component
Authors: Kwon Meeae Y. , Gu Mai
Published: January 2021

True malignant mixed tumor (carcinosarcoma) of the salivary gland is an extremely rare tumor. By definition, it is composed of both malignant epithelial and malignant mesenchymal elements. The most common type of the former is squamous cell carcinoma or adenocarcinoma and the most common type of the latter is chondrosarcoma, followed in frequency by fibrosarcoma, leiomyosarcoma, osteosarcoma, and in rare instances liposarcoma. We report a case of true malignant mixed tumor of the parotid gland in association with a pleomorphic adenoma in a 47-year-old man that contained a very unusual type of malignant mesenchymal component, rhabdomyosarcoma. Cytologic and histologic features and immunohistochemical results are presented. In addition, the literature is reviewed, and the possible histogenesis and pathogenesis of malignant mixed tumor of the salivary gland are briefly discussed.
Rectal Pulse Granuloma
Authors: Pereira Telma C. , Prichard Jeffrey W. , Khalid Mushtaq , Medich David S. , Silverman Jan F.
Published: January 2021

Pulse granuloma is a rare benign entity, most likely representing a foreign body reaction to vegetable particles. We report a case of a pulse granuloma involving the rectum. The patient presented with a submucosal and intramuscular mass lesion found at routine rectal examination and subsequent colonoscopy. The mass was excised and the microscopic examination revealed acute and chronic inflammatory cells, foreign-body giant cells, vegetable matter, and convoluted hyaline rings and scattered circular structures containing basophilic granules, consistent with pulse granuloma. There are a few reports in the literature of pulse granulomas, with most occurring in the oral cavity or lungs. To the best of our knowledge, this is the first reported example of pulse granuloma in the rectum. Although rare, familiarity with this entity's distinctive histopathologic features may avoid a delay in diagnosis and prevent the expense of distinguishing it from its histologic lookalikes.
Evaluation of Characteristics Associated With Acute Splenitis (Septic Spleen) as Markers of Systemic Infection
Authors: Feig James A. , Cina Stephen J.
Published: January 2021

Context.—Acute splenitis, also known as acute splenic tumor or septic spleen, is loosely defined as a neutrophilic infiltrate and congestion within the red pulp accompanied by splenomegaly. Standard pathology texts state that the histologic finding of acute splenitis is reflective of septic states. However, this association has seldom been tested in the medical literature.

Objective.—The purpose of this study was to determine if sepsis can be predicted by the presence of quantitative characteristics used to identify acute splenitis.

Methods.—The postmortem splenic tissue of 20 clinically diagnosed cases of sepsis and 20 noninfectious control cases were retrospectively examined in a blinded fashion for amount of neutrophilic infiltration, weight (obtained from autopsy report), and presence of congestion.

Results.—No significant correlation could be found between the parameters of neutrophilic infiltrate or splenic weight and clinically diagnosed septicemia. The presence of splenic congestion was unexpectedly found to be more likely with noninfectious causes of death.

Conclusion.—Acute splenitis is presently ill defined, and no available evidence convincingly shows that its presence suggests a septic state.
Myeloperoxidase-Positive Intravascular Large B-Cell Lymphoma
Authors: Conlin Phillip A. , Orden Mageline B. , Hough Tiffany R. , Morgan David L.
Published: January 2021

Intravascular large B-cell lymphoma (IVLBL) is an uncommon form of non-Hodgkin lymphoma that is also known as malignant angioendotheliosis, intravascular lymphomatosis, and angiotropic large-cell lymphoma. The disease is characterized by a bizarre population of neoplastic cells, which are found systemically within vascular lumina. Although originally thought to be a neoplastic process of the endothelial cells, it has since been demonstrated, by molecular techniques and immunohistochemistry, that the neoplastic cells are of lymphoid origin. The differential diagnosis of these lesions includes granulocytic sarcomas that can be distinguished from IVLBL or other lymphomas by the presence of immunohistochemical positivity for myeloperoxidase. We describe a patient with a history of a myelodysplastic syndrome who subsequently developed IVLBL, which demonstrated immunohistochemical positivity for myeloperoxidase. To our knowledge, this represents the first case of a malignant lymphoma to demonstrate such findings.
Diagnostic Utility of Intracytoplasmic Lumen and Transgressing Vessels in Evaluation of Hürthle Cell Lesions by Fine-Needle Aspiration
Authors: Yang Yi J. , Khurana Kamal K.
Published: January 2021

Introduction.—Recent abstracts have emphasized the importance of recognizing intracytoplasmic lumen and transgressing vessels as useful criteria enabling distinction between Hürthle cells encountered in neoplastic and nonneoplastic thyroid aspirates. The purpose of this retrospective study was to evaluate if application of these criteria improves specificity and sensitivity of cytologic diagnosis of true Hürthle cell neoplasms.

Materials and Methods.—We retrospectively reviewed 30 fine-needle aspirates of thyroid with cytologic diagnosis of Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid with prominent Hürthle cells (17 cases). All cases were evaluated for the presence of intracytoplasmic lumen and transgressing vessels and were reclassified as neoplastic or nonneoplastic based on the presence or absence of 1 or both of these criteria. Surgical follow-up was available in all cases.

Results.—Surgical follow-up in 13 cases of Hürthle cell neoplasms revealed Hürthle cell carcinoma (3 cases), Hürthle cell adenoma (6 cases), and Hashimoto's thyroiditis (4 cases). Seventeen cases with nonneoplastic diagnosis revealed Hürthle cell carcinoma (1 case), Hashimoto's thyroiditis (12 cases), and nodular goiter (4 cases). After application of the previously mentioned cytologic criteria, the cytologic diagnoses were reclassified as Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid (17 cases). The true sensitivity of the test before and after the application of the criteria was 90% and 100%, respectively. The true specificity before and after the application of the cytologic criteria was 65% and 85%, respectively.

Conclusions.—Intracytoplasmic lumen and transgressing vessels are helpful features in distinguishing neoplastic and nonneoplastic Hürthle cell thyroid lesions. Use of these criteria may improve the specificity and sensitivity of the cytologic diagnosis.
Cytokeratin Subset Immunostaining in Rectal Adenocarcinoma and Normal Anal Glands
Authors: Ramalingam Preetha , Hart William R. , Goldblum John R.
Published: January 2021

Context.—A large percentage of cases of perianal Paget disease are associated with an internal cancer, most commonly rectal adenocarcinoma. Immunostains for cytokeratin 7, cytokeratin 20, and gross cystic disease fluid protein 15 are useful in identifying cases associated with rectal adenocarcinoma. The Paget cells and rectal adenocarcinoma cells of these lesions typically have a cytokeratin 7+/cytokeratin 20+/gross cystic disease fluid protein 15− immunophenotype. It is not known whether rectal adenocarcinoma unassociated with perianal Paget disease has the same cytokeratin profile as rectal adenocarcinoma associated with perianal Paget disease.

Objective.—To evaluate the immunohistochemical cytokeratin 7 and 20 profile of resected rectal adenocarcinoma unassociated with perianal Paget disease as well as that of normal anal glands from hemorrhoidectomy specimens.

Design.—We performed immunohistochemistry for cytokeratins 7 and 20 on tissues from 30 cases of rectal adenocarcinoma unassociated with perianal Paget disease and 12 hemorrhoidectomy specimens from 12 cases with normal anal glands. We defined positive staining as any immunoreactivity within the neoplastic cells.

Results.—Twenty-six of 30 cases of rectal adenocarcinoma (87%) had a cytokeratin 7−/cytokeratin 20+ immunophenotype, similar to the immunophenotype of cases of nonrectal large intestine adenocarcinoma. In 4 cases (13%), neoplastic cells coexpressed cytokeratins 7 and 20. Anal glands stained strongly for cytokeratin 7 but were negative for cytokeratin 20 in all cases, and the anal transitional zone mucosa had a similar immunophenotype.

Conclusions.—Rectal adenocarcinoma unassociated with perianal Paget disease has a cytokeratin profile similar to that of nonrectal large intestine adenocarcinoma. These data suggest that rectal adenocarcinoma unassociated with perianal Paget disease has a different cytokeratin profile than rectal adenocarcinoma associated with perianal Paget disease.
Endometrial Stromal Sarcoma of the Rectosigmoid Colon Arising in Extragonadal Endometriosis and Revealed by Portal Vein Thrombosis
Authors: Mourra Najat , Tiret Emmanuel , Parc Yann , de Saint-Maur Paul , Parc Rolland , Flejou Jean-François
Published: January 2021

Malignant transformation is an infrequent complication of endometriosis. The ovary is the primary site in 76% of cases, and extragonadal sites are identified in 24%. Endometrioid carcinoma is the most common histologic type; sarcoma is very rare. We report a case of low-grade endometrial stromal sarcoma of the rectosigmoid colon presenting with epigastric pain due to portal vein thrombosis. This tumor arose from extragonadal endometriosis in a 61-year-old woman and was treated by surgical resection. The main differential diagnosis of this unusual colonic neoplasm includes primary mesenchymal tumors, such as gastrointestinal stromal tumors.
Colonic Lymphoid Hyperplasia in Melanosis Coli
Authors: Pearce Callum B. , Martin Hilary , Duncan Hamish D. , Goggin Patrick M. , Poller David N.
Published: January 2021

We describe the case of a patient with Rett syndrome, a syndrome characterized by progressive infant encephalopathy, developmental delay, dementia, autism, ataxia, microcephaly, spastic paraparesis, and autonomic neuropathy with constipation. At colonoscopy, multiple foci of tiny white, sessile, polypoid lesions were seen throughout the colon and rectum, mimicking the appearances of small hyperplastic or adenomatous polyps, associated with generalized melanosis coli. This is the first case to our knowledge describing melanosis coli in a patient with Rett syndrome. As melanosis pigment deposition is characteristically not seen in lymphoid tissue, the lymphoid tissue was identifiable at endoscopy as multiple white nodules mimicking generalized colonic polyposis throughout the colon. We discuss the likely mechanisms of lymphoid hyperplasia and coexistent melanosis coli in Rett syndrome.
Diagnosis of Chondroid Lipoma by Fine-Needle Aspiration Biopsy
Authors: Yang Yi Jun , Damron Timothy A. , Ambrose Joseph L.
Published: January 2021

Chondroid lipoma is a rare, recently described soft tissue tumor that mimics extraskeletal chondrosarcoma and myxoid liposarcoma. Reports regarding its cytologic and radiological features are sparse. In this report, we describe the cytologic features of this unusual tumor, which include mixed mature lipocytes and lipoblast-like cells embedded in chondromyxoid matrix. We also describe the “target sign appearance” of this tumor in magnetic resonance imaging studies, resembling a neurogenic tumor. More importantly, we demonstrate that a definitive diagnosis of this unusual tumor can be made by fine-needle aspiration biopsy. The usefulness of cell block in fine-needle aspiration biopsy diagnosis of soft tissue tumors is emphasized.
A High-Grade Primary Leiomyosarcoma of the Bladder in a Survivor of Retinoblastoma
Authors: Liang Sharon X. , Lakshmanan Yegappan , Woda Bruce A. , Jiang Zhong
Published: January 2021

Second nonocular malignancies develop with increased incidence in patients with hereditary retinoblastoma. Osteosarcoma is by far the most common type with an incidence of up to 50%, followed by soft tissue sarcomas. Visceral leiomyosarcoma is extremely rare and only 2 cases have been reported in the past 2 decades, one in the liver and another one in the urinary bladder, both of which developed after cyclophosphamide therapy. Here we report a case of vesical leiomyosarcoma that was diagnosed in a 49-year-old woman 47 years after the diagnosis of a hereditary retinoblastoma. The patient's retinoblastoma was treated with unilateral enucleation without adjuvant radiation or chemotherapy. We believe that this is the first report of vesical leiomyosarcoma occurring in a patient with retinoblastoma without a prior history of radiation or chemotherapy. This report is significant not only because of the rarity of vesical leiomyosarcoma as a second nonocular tumor in retinoblastoma patients, but also because of the infrequency of vesical leiomyosarcoma in general. We also investigated the potential molecular pathogenesis of the leiomyosarcoma.
Clear Cell Variant of Fibrolamellar Carcinoma of the Liver
Authors: Cheuk Wah , Chan John K. C.
Published: January 2021

Fibrolamellar carcinoma of the liver is a distinctive variant of hepatocellular carcinoma characterized histologically by trabeculae of oncocytic cells with intervening lamellae of collagen fibers. We describe a case with a prominent component of clear cells, a feature not previously recognized in this tumor type. The patient was a 59-year-old woman incidentally found to have a solitary liver tumor, measuring 5 cm. Pathologic examination revealed a circumscribed, firm, tan tumor with peculiar concentric streaks. Oncocytic cells and clear cells were arranged in trabeculae separated by lamellae of collagen or sinusoids. The clear cells possessed abundant finely reticulated clear cytoplasm, which was highlighted by trichrome stain and immunostaining with antimitochondria antibody. Ultrastructurally, the cytoplasm of the clear cells was packed with empty membrane-bound vesicles that occasionally contained short cristae. The features suggested that the clear cell change resulted from ballooning and rarefactive changes of mitochondria. Clear cell fibrolamellar carcinoma should not be confused with conventional clear cell hepatocellular carcinoma, since the former is associated with a more favorable prognosis.
Nongynecologic Cytology Turnaround Time
Authors: Jones Bruce A. , Novis David A.
Published: January 2021

Objectives.—To determine the turnaround time for nongynecologic cytology and to identify laboratory and specimen characteristics associated with variations in turnaround time.

Design and Setting.—Prospective evaluation of nongynecologic cytology turnaround times in 180 laboratories.

Main Outcome Measure.—Nongynecologic cytology case turnaround time.

Results.—Participants from 180 laboratories submitted turnaround times for 16 950 nongynecologic cytology cases and submitted information describing their laboratories' practice characteristics relating to the processing of nongynecologic cytology specimens. Half of the participating laboratories had mean receipt to report turnaround times of 1.6 calendar days or less and were able to complete 90% of their cases within 3.0 calendar days. Ten percent of participants had mean turnaround times greater than 3.2 days and required 6.0 or more days to report 90% of their cases. Longer turnaround times were associated with processing fluid and fine-needle aspiration specimens, issuing atypical/suspicious for malignancy and nondiagnostic diagnoses, having cytotechnologist students screen slides, having to contact the physician offices for additional information, having to retrieve prior case material for review, and having to perform cell blocks and/or special stains.

Conclusion.—There is an opportunity for laboratories to shorten nongynecologic turnaround time by altering certain laboratory practices.
Method Preferences and Test Accuracy of Antimicrobial Susceptibility Testing
Authors: Jones Ronald N.
Published: January 2021

Objective.—To summarize the antimicrobial susceptibility testing results from the College of American Pathologists (CAP) Microbiology Surveys Program for 2000. Specifically, the frequency of tests used and the quantitative and qualitative (susceptibility category) accuracy were assessed.

Design.—The CAP Microbiology Surveys challenged subscribers in 2000 with 3 well-characterized organisms for antimicrobial susceptibility testing in pure culture. Each laboratory was to use the test method and reporting procedures routinely applied to patient samples. The strains were National Committee for Clinical Laboratory Standards (NCCLS) quality control organisms with precisely defined antimicrobial susceptibility patterns and reproducibility. Results reported by participants (2685–2979/sample) were graded for categorical accuracy and quantitative performance by comparing reported minimal inhibitory concentrations (μg/mL) or zone diameters (mm) against quality control ranges published by the NCCLS. The appropriateness of reported drugs was determined in the context of the type and anatomic location of the infection.

Results.—The tests most often used varied by the species of the organism and growth characteristics of the isolated strains. Nonfastidious, rapid-growing Surveys unknowns (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) were most often tested with commercial systems (MicroScan, 42.0%–42.4%; Vitek, 41.5%–43.0%) or with the standardized disk diffusion method (12.8%–13.9%). In contrast, fastidious species, such as Streptococcus pneumoniae (ATCC 49619), were predominantly tested by Etest (40.3%), followed by disk diffusion (27.6%) and MicroScan (23.2%). Categorical accuracy was essentially equal between dilution (98.9%) and diffusion (99.0%) methods. Among the minimal inhibitory concentration methods used to test penicillin against S pneumoniae, Etest method quantitative accuracy (96.3%) was greater than that of MicroScan (92.4%). Quantitative accuracy was greatest for dilution minimal inhibitory concentration methods, with more than 90% of results within NCCLS quality control ranges for nearly all reported antimicrobials. Reevaluations of quality control ranges may be needed for 4 to 7 agents, depending on method. Reporting errors were also detected in 2 areas: (1) reporting results for drugs not active at the site of infection and (2) reporting results for drugs tested with suboptimal methods without published NCCLS interpretive criteria.

Conclusions.—Antimicrobial susceptibility testing methods used in US laboratories were dominated by commercial products with relatively high accuracy (qualitative and quantitative). As available methods have become better suited to both fastidious and rapid-growing species, reporting errors have assumed a higher level of concern to the CAP Surveys in an effort to minimize prescription errors.
Nesidioblastosis Coexisting With Islet Cell Tumor and Intraductal Papillary Mucinous Hyperplasia
Authors: Zhao Xiaohui , Stabile Bruce E. , Mo Junqin , Wang Jun , French Samuel W.
Published: January 2021

A coexisting of intraductal papillary mucinous hyperplasia (IPMH) and islet cell tumor with nesidioblastosis of the pancreas in a 51-year-old man is reported. All of the clinical data indicated an insulinoma. A distal pancreatectomy was performed. A discrete mass measuring 1.9 × 2.0 cm was grossly identified in the tail of the pancreas. There were no other gross lesions. An islet cell tumor with nesidioblastosis was confirmed by immunostains and ultrastructural study. In addition, an IPMH was found that involved mainly branches of the pancreatic duct. The islet cell tumor and IPMH were topographically separated; however, there was a histologically intimate relationship between the nesidioblastosis and the IPMH. These findings indicate that the IPMH may have derived from autocrine and paracrine influences on the existing duct epithelial cells. To the best of our knowledge, this is the first report of nesidioblastosis coexisting with islet cell tumor and IPMH.
Extraskeletal Ewing Sarcoma in a 77-Year-Old Woman
Authors: Cheung Carol C. , Kandel Rita A. , Bell Robert S. , Mathews Raymond E. , Ghazarian Danny M. D.
Published: January 2021

Extraskeletal Ewing sarcoma (EES) is a rare soft tissue tumor that is morphologically indistinguishable from Ewing sarcoma of bone. It is usually found in young people, but several cases have occurred in patients older than 50 years. The differential diagnoses include other small, blue round cell tumors (SBRCTs) and other members of the Ewing family of tumors such as the primitive neuroectodermal tumor. We present a case of EES in the left inguinal region of a 77-year-old woman. The tumor was distinguished from other SBRCTs by lack of immunoreactivity for epithelial, lymphoid, vascular, neuroendocrine, neural, histiocytic, and muscle markers. Primitive neuroectodermal tumor was excluded because of the lack of neural differentiation by histologic analysis, immunohistochemistry, and electron microscopy. Extraskeletal Ewing sarcoma was confirmed by characteristic features on histologic analysis, histochemistry, immunohistochemistry, and electron microscopy and by the presence of the t(11;22)(q24;q12) fusion transcript detected by reverse transcriptase–polymerase chain reaction. This case serves to remind the reader that EES is not a tumor that occurs exclusively in young patients.
p53 Mutation in Adenocarcinoma Arising in Retrorectal Cyst Hamartoma (Tailgut Cyst)
Authors: Moreira Andre L. , Scholes John V. , Boppana Sushma , Melamed Jonathan
Published: January 2021

Retrorectal cyst hamartoma (RCH) is a rare benign cystic lesion located in the retrorectal space. Malignancy arising in such lesions is very uncommon. In this study, 2 cases of mucinous adenocarcinoma arising in RCH are presented. In one case, dysplastic epithelium lined the cyst wall, surrounding the area of carcinoma and suggesting a dysplasia-carcinoma progression in RCH. Adenocarcinoma and the dysplastic epithelium were strongly positive for p53 and Ki-67 and showed negative staining for p21 by immunohistochemistry. These findings are suggestive of a mutation in the p53 gene in the adenocarcinoma and in dysplastic epithelium lining the cysts, similar to the dysplasia-carcinoma sequence described for the development of colonic adenocarcinoma.
Digital Image Documentation for Quality Assessment
Authors: Cruz Domingos , Valentí Carla , Dias Aureliano , Seixas Mário , Schmitt Fernando
Published: January 2021

Objective.—To demonstrate the feasibility of the use of digital images to document routine cases and to perform diagnostic quality assessment.

Methods.—Pathologists documented cases by acquiring up to 12 digital images per case. The images were sampled at 25:1, 50:1, 100:1, 200:1, or 400:1 magnifications, according to adequacy in aiding diagnosis. After each acquisition, the referral pathologist marked a region of interest within each acquired image in order to evaluate intrinsic redundancy. The extrinsic redundancy was determined by counting the unnecessary images. Cases were randomly selected and reviewed by one pathologist. The quality of each image, the possibility of accomplishing a diagnosis based on images, and the degree of agreement was evaluated.

Results.—During routine practice, 1469 cases were documented using 3902 images. Most of the images were acquired at higher power magnifications. From all acquired cases, 143 cases and their 373 related images were randomly selected for review. In 88.1% (126/143) of reviewed cases, it was possible to accomplish the diagnosis based on images. In 30.2% (38/126) of these cases, the reviewer considered that the diagnosis could be accomplished with fewer images. The referral pathologist and the reviewer found intrinsic redundancy in 57.8% and 54.5% of images, respectively.

Conclusions.—Our results showed that digital image documentation to perform diagnostic quality assessment is a feasible solution. However, owing to the impact on routine practice, guidelines for acquisition and documentation of cases may be needed.
Computed Tomographic–Pathologic Correlation of Gross Tumor Volume and Clinical Target Volume in Non–Small Cell Lung Cancer
Authors: Chan Roscoe , He Yu , Haque Abida , Zwischenberger Joseph
Published: January 2021

Context.—Computed tomographic (CT) scan data are used regularly in radiation treatment planning for patients with lung cancer. To our knowledge, the relationship of the CT images of tumors and their corresponding microscopic extent has not yet been studied in detail.

Objective.—To correlate tumor sizes on CT with tumor sizes measured microscopically (ie, the gross tumor volume [GTV]-clinical target volume margin) in non–small cell lung cancers.

Design.—Prospective pilot study.

Setting.—Single institution.

Patients.—Patients with operable non–small cell lung cancer were identified preoperatively.

Interventions.—Once the surgical specimen was available, it was oriented with the surgeon and the pathologist. Seven whole-mount, cross-sectional histologic glass slides were made from 5 tumors using formalin fixation and hematoxylin-eosin staining. The pathologist then outlined the cancer-containing area under the microscope (Micro-GTV) and the area of surrounding inflammatory response (Micro-GTV + inflammation). Preoperative CT scans were used for outlining tumor on the corresponding slice (CT-GTV).

Main Outcome Measures.—Correlation of the areas of Micro-GTV, Micro-GTV + inflammation, and CT-GTV was performed.

Results.—There was an obvious trend that the CT-GTV was bigger than the Micro-GTV, except in specimen 1, in which the 2 areas were about equal. However, on comparing the values for the CT-GTV and the Micro-GTV + inflammation, the difference between the 2 areas became smaller.

Conclusions.—Modern CT scans might overestimate the GTV in non–small cell lung cancer. The GTV–clinical target volume margin could actually be zero or even a negative value. The findings in this small study are interesting and provoking. Further study with a larger number of patients and more rigid quality control is warranted to confirm our findings.
Peculiar Artifacts Mimicking Carcinoma
Authors: Wu Mark Li-cheng , Natarajan Sathima , Lewin Klaus J.
Published: January 2021

Artifacts that mimic malignancy may lead to diagnostic difficulty and can cause serious consequences. We present 2 cases received in consultation which demonstrated peculiar artifacts that closely mimicked carcinoma. In case 1, contaminating products of conception were confused with squamous cell carcinoma. In case 2, artifactual signet ring cells induced by procedural trauma were suspicious for signet ring cell carcinoma. In both cases, clinical correlation failed to completely exclude carcinoma, and limited tissue prevented use of ancillary studies. Our final resolution of these artifacts required lengthy and detailed morphologic analysis.
Anomalous Origin of 4 Coronary Ostia From the Right Sinus of Valsalva in a Patient With Hypertrophic Cardiomyopathy
Authors: Beach Lynn , Burke Allen , Chute Dennis , Virmani Renu
Published: January 2021

Anomalous origin of 4 separate coronary ostia from a single coronary sinus has rarely been reported. We report what is to our knowledge a previously undescribed variation characterized by the left anterior descending, left ramus, left circumflex, and right coronary arteries originating from separate ostia in the right sinus of Valsalva. In addition, the autopsy disclosed features of hypertrophic cardiomyopathy, rarely associated with congenital coronary anomalies.
Benign Myoepithelioma of the Lung
Authors: Veeramachaneni Ravindra , Gulick Janis , Halldorsson Ari O. , Van Thanh T. , Zhang Ping L. , Herrera Guillermo A.
Published: January 2021

This report describes a benign myoepithelioma of the lung that occurred in a 60-year-old woman. The patient had experienced hoarseness for 6 weeks, and a computed tomographic scan showed a nodule of approximately 2 cm in diameter at the peripheral portion of her right upper lung. Positron emission tomography showed no uptake of F-18 fluorodeoxyglucose in the nodule. Wedge biopsy of the lesion showed benign spindle cells arranged in a whorled pattern. The cells were positive for both cytokeratin and smooth muscle actin, which corresponded to the presence of tonofilaments and myofilaments that were identified ultrastructurally. The features of the present case of benign myoepithelioma that differ from features of previously reported benign and malignant cases of myoepithelioma in the lung are discussed in the report.
Collagenous Gastritis Associated With Lymphocytic Gastritis and Celiac Disease
Authors: Stancu Mirela , De Petris Giovanni , Palumbo Theodore P. , Lev Robert
Published: January 2021

Collagenous gastritis is a rare disorder, with only 8 cases reported in the literature, 2 in children and 6 in adults. We report an additional case of collagenous gastritis in a 42-year-old man with celiac disease. A thickened (>10 μm) subepithelial collagen band with entrapped capillaries, fibroblasts, and inflammatory cells was seen in the stomach, associated with lymphocytic gastritis. The duodenal mucosa showed severe villous atrophy but no subepithelial collagen deposition. No evidence of lymphocytic or collagenous colitis was found in the colon. The patient became symptom-free on a gluten exclusion diet and showed partial improvement of histopathologic findings after 3 months. Collagenous gastritis is a rare disease, but a wider recognition of its histopathologic features and clinical associations may bring more cases to light and provide additional clues in determining its etiology and pathogenesis.
Primary Gastric Choriocarcinoma
Authors: Liu Zhi , Mira Jose L. , Cruz-Caudillo Jose C.
Published: January 2021

Choriocarcinoma is a rapidly invasive, widely metastatic human chorionic gonadotropin (HCG)–producing neoplasm, usually intrauterine and gestational. Primary gastric choriocarcinoma is very rare, and its pathogenesis is still uncertain. We report a case of primary gastric choriocarcinoma associated with adenocarcinoma in a 36-year-old woman. The patient presented with gastrointestinal bleeding and a gastric mass clinically suspicious of gastric adenocarcinoma. Histopathologic evaluation proved the tumor to be a choriocarcinoma, with a minor component of a poorly differentiated adenocarcinoma. The patient was treated with a standard nongestational choriocarcinoma chemotherapy regimen. An impressive initial response was evidenced by clinical reduction of the tumor volume and drop of the serum β-HCG levels after the first cycle. However, the tumor rapidly recurred in the abdomen and disseminated to the lungs, which were documented by new elevation of serum β-HCG levels and computed tomographic scans despite continuing with 3 more cycles of chemotherapy. The patient died 6 months after diagnosis.
Routine Outpatient Laboratory Test Turnaround Times and Practice Patterns
Authors: Steindel Steven J. , Jones Bruce A.
Published: January 2021

Objectives.—To determine baseline parameters for routine outpatient test turnaround time (TAT), to identify influential factors, and to study the impact of managed care on this testing.

Method.—Using forms supplied by the College of American Pathologists Q-Probes program, laboratories conducted a self-directed study of routine outpatient TATs over a 4-week period. Data requested included various times of day associated with the collection, laboratory receipt, and result verification of specimens, as well as details on the drawing location and ordering and delivery methods for up to 3 tests, namely, a complete blood cell count (CBC), biochemical profile, or thyrotropin test. For the CBC, an indication was requested if a manual differential was performed. Additionally, practice-related questions were asked, including several about whether the laboratory was associated with a managed care organization (MCO). The main outcome measures included the components of the TAT process and related factors.

Participants.—Six hundred nineteen laboratories from those enrolled in the 1997 College of American Pathologists Q-Probes program.

Results.—Data were submitted by 614 participants, most US hospitals, and represented 30 240 CBCs, 25 683 biochemical profiles, and 14 801 thyrotropins. Collection to verification TATs increased for specimens received later in the day for all analytes, but the magnitude of the increase was greatest for thyrotropin. Collection to laboratory receipt TAT was similar for all analytes, but the time and distribution increased with time of day. Testing time (receipt to verification) was similar for the CBC and biochemical profile, but was greatly increased for thyrotropin. Most participants tested the CBC and the biochemical profile as they arrived, but many delayed testing for thyrotropin. Most (70%) outpatient specimens were collected within the institution; only about 10% came from local physicians' offices. A median 46.7% of hospital testing involved outpatients. Only 10% of laboratories operated under an MCO; these laboratories reported a median of 45% of specimens coming from their MCO. Being associated with an MCO increased TAT for the CBC and biochemical profile.

Conclusions.—Outpatient testing comprises about half of all hospital testing, yet systems are not optimized. Preanalytic TAT increases during the day, which indicates increasing delays in the collection and transport stages. Imposition of a test schedule on thyrotropin results in a delay pattern that is very different from the CBC and biochemical profile, which are tested on arrival. A laboratory's association with an MCO had a weak impact on TAT.
Use of FTA Gene Guard Filter Paper for the Storage and Transportation of Tumor Cells for Molecular Testing
Authors: Dobbs Larry J. , Madigan Merle N. , Carter Alexis B. , Earls Lori
Published: January 2021

Context.—Efficient methods of storing tumor specimens for molecular testing are needed in the modern surgical pathology laboratory. The FTA Gene Guard system is a novel method for the collection and room temperature storage of blood samples for DNA testing. The method uses index card–sized filter papers that provide an ideal medium on which to store tumor specimens for DNA testing.

Objective.—To determine whether FTA filter paper can be used in the surgical pathology laboratory to store tumor cells for DNA testing.

Design.—Cell suspensions were prepared from 60 surgical specimens, and DNA was extracted either immediately or after storage on FTA paper. The DNA extracted by each method was tested by polymerase chain reaction (PCR) for the β-globin and interferon gamma genes, and the results were compared. Fifteen lymph node specimens stored on FTA paper were then tested for immunoglobulin heavy chain (IgH) gene rearrangement by PCR, and these results were compared with those obtained for immediately extracted DNA.

Setting.—University medical center.

Results.—The DNA extracted from cells stored on FTA paper performed as well in the PCR as the freshly extracted DNA in nearly all cases (>95%). The results of tests for IgH gene rearrangements showed 100% concordance between the 2 methods of DNA extraction.

Conclusion.—Cells from surgical specimens can be stored on FTA paper for extended lengths of time, and DNA can be extracted from these cells for PCR-based testing. FTA filter paper is a reliable medium for the storage and/or transport of tumor cells for PCR-based DNA analysis.
Mycobacterium mucogenicum Isolated From a Patient With Granulomatous Hepatitis
Authors: Goldblatt Mark R. , Ribes Julie A.
Published: January 2021

Mycobacterium mucogenicum is a recently characterized, rapid-growing mycobacteria rarely seen in human infections. We describe the case of a 51-year-old man with rapidly progressive granulomatous hepatitis caused by M mucogenicum. Although premortem evaluation failed to identify an etiologic agent, autopsy liver cultures produced smooth, rapid-growing mycobacterial colonies. Biochemical, growth, and cell wall fatty acid characteristics were consistent with the identification of M mucogenicum.
The Laboratory Diagnosis of Platelet Disorders
Authors: Kottke-Marchant Kandice , Corcoran George
Published: January 2021

Objective.—To provide both a detailed description of the laboratory tests available in the diagnosis of platelet disorders and a testing algorithm, based on platelet count, that can be used to direct the evaluation of platelet disorders.

Data Sources.—A literature search was conducted using the National Library of Medicine database.

Study Selection.—The literature on laboratory testing of platelet function was reviewed.

Data Extraction and Data Synthesis.—Based on the literature review, an algorithm for platelet testing was developed.

Conclusions.—A history of mucocutaneous bleeding often indicates abnormal platelet function that can be associated with a normal, increased, or decreased platelet count. Multiple laboratory procedures can now be used to determine the underlying pathologic condition of platelet dysfunction when other deficiencies or defects of the coagulation cascade or fibrinolysis are ruled out. Simple procedures, such as platelet count, peripheral blood smear, and a platelet function screening test, will often lead the investigator to more specific analyses. Although platelet function testing is often limited to larger medical centers with highly trained technologists, newer technologies are being developed to simplify current procedures and make platelet function testing more accessible. This review provides an algorithm for platelet testing that may be of benefit to pathologists and physicians who deal with hemostatic disorders.
Do Proficiency Testing Participants Learn From Their Mistakes?
Authors: Novak Robert W.
Published: January 2021

Context.—Participation in proficiency testing is required under the Clinical Laboratory Improvement Amendments of 1988. Although the primary purpose of this testing is evaluation of current laboratory performance, a major secondary benefit of such testing is postulated to be progressive improvement in laboratory performance over time as laboratories learn from their previous experiences and feedback.

Objective.—To test the hypothesis that a secondary result of proficiency testing is improvement over time of laboratory performance.

Design.—The performance of participants in a large proficiency testing program (EXCEL), designed for clinic and office laboratories, on a specific problematic competence, the ability to differentiate group A streptococcus from group C streptococci, was monitored during a 6-year period (1996–2001) for changes in participant performance.

Interventions.—With each testing cycle, feedback on performance relative to peers and an educational discussion analyzing performance and suggesting best practices was submitted to participants.

Results.—Despite consistent feedback, there was no significant change in participant performance throughout the period studied.

Conclusions.—In a large, stable proficiency testing program, a significant throat culture competence, which demonstrated less than optimal performance, did not improve over time, suggesting that current utilization of proficiency testing results in laboratory improvement programs is suboptimal.
Mitochondrial DNA–Related Mitochondrial Dysfunction in Neurodegenerative Diseases
Authors: Swerdlow Russell H.
Published: January 2021

Mitochondrial dysfunction occurs in several late-onset neurodegenerative diseases. Determining its origin and significance may provide insight into the pathogeneses of these disorders. Regarding origin, one hypothesis proposes mitochondrial dysfunction is driven by mitochondrial DNA (mtDNA) aberration. This hypothesis is primarily supported by data from studies of cytoplasmic hybrid (cybrid) cell lines, which facilitate the study of mitochondrial genotype-phenotype relationships. In cybrid cell lines in which mtDNA from persons with certain neurodegenerative diseases is assessed, mitochondrial physiology is altered in ways that are potentially relevant to programmed cell death pathways. Connecting mtDNA-related mitochondrial dysfunction with programmed cell death underscores the crucial if not central role for these organelles in neurodegenerative pathophysiology. This review discusses the cybrid technique and summarizes cybrid data implicating mtDNA-related mitochondrial dysfunction in certain neurodegenerative diseases.
Human Lymphocyte Antigen Molecular Typing
Authors: Gerlach John A.
Published: January 2021

The human lymphocyte antigen (HLA) typing community was one of the early groups to adopt molecular testing. This action was borne out of the need to identify the many alleles of the highly polymorphic HLA system. Early paradigms used restriction fragment length polymorphism regimes, but the polymerase chain reaction method of amplification quickly replaced that less-than-discriminating choice. Methods currently in use for HLA typing, with commercial kits available, are sequence-specific oligonucleotide probe (both dot blot and the reverse blot dot), sequence-specific primer amplification, restriction fragment length polymorphism of amplified products, double-stranded sequence conformation polymorphism (with and without reference strand), sequence-based typing, and microarray technologies. More than 1250 alleles are recognized by the World Health Organization and meet their criteria for assignment. These alleles can be identified by molecular methods and represent alleles present at class I and class II loci of the HLA complex. On occasion, ambiguous results still persist, even with the best molecular typing methods. Therefore, it is clear to the HLA typing community that a combination of the above methods may be needed to allow true discrimination of the possible alleles an individual carries in their genetic makeup. It is also clear that a typing laboratory may need to resort to nonmolecular serology to understand the significance and impact of the type generated by the HLA molecular typing laboratory.
Genetic Polymorphisms Associated With Venous and Arterial Thrombosis
Authors: Kottke-Marchant Kandice
Published: January 2021

Objective.—To provide an overview of genetic polymorphisms associated with thrombotic cardiovascular disease.

Data Sources.—A literature search using the National Library of Medicine database.

Study Selection.—The literature on genetic polymorphisms associated with venous and arterial thrombosis was reviewed.

Data Extraction.—Based on the literature review, the clinical significance of polymorphisms in various coagulation proteins was assessed and a summary was developed.

Conclusions.—Thrombosis is a multifactorial disorder, with both congenital and acquired risk factors. It is now clear that there are many genetic abnormalities that impart an increased risk for thrombophilia, and the presence of more than 1 abnormality results in a further increased risk of thrombosis. In hemostasis, there is a balance between procoagulant factors and natural anticoagulant proteins. The first genetic thrombotic disorders described were deficiencies of the natural anticoagulants, such as antithrombin, protein C, and protein S, but these abnormalities are rare and are caused by many different mutations. More recently, single polymorphisms that are relatively common in the general population have been described in procoagulant factors, such as factor V and prothrombin, which impart an increased risk for venous thrombosis. As more scrutiny is placed on the hemostatic system, further polymorphisms have come to light. The current challenge is to elucidate the relationship between these new polymorphisms and either venous or arterial thrombotic cardiovascular disease.
Trends in Genomic Analysis of the Cardiovascular System
Authors: Moldovan Leni , Moldovan Nicanor I.
Published: January 2021

Objective.—To evaluate the opportunities afforded cardiovascular medicine by the comprehensive and integrative approaches of genomics in cellular physiology. We present a meta-analysis of recently reported results obtained by means of high-throughput technologies (complementary DNA and oligonucleotide arrays, serial analysis of gene expression [SAGE]), as well as more traditional molecular biology approaches (real-time polymerase chain reaction, differential display, and others).

Data Sources.—Newly published articles identified on PubMed and additional data provided by authors on-line (where available).

Conclusions.—The impact of genomic analysis on cardiovascular research is already visible. New genes of cardiovascular interest have been discovered, while a number of known genes have been found to be changed in unexpected contexts. The patterns in the variation of expression of many genes correlate well with the models currently used to explain the pathogenesis of cardiovascular diseases. Much more work has yet to be done, however, for the full exploitation of the immense informative potential still dormant in the genomic technologies.
Clinical Trials in Vascular Gene Therapy
Authors: Simari Robert D. , O'Brien Timothy
Published: January 2021

Objective.—Vascular gene transfer provides unique opportunities for novel therapies for cardiovascular disease. To define the limitations and expectations of translating preclinical strategies to clinical therapy, the kinetics and extent of vascular transgene expression must be determined.

Data Sources.—Published clinical and preclinical studies of vascular gene transfer.

Data Extraction.—Kinetics and extent of vascular transgene expression.

Data Synthesis.—In spite of ongoing clinical studies in vascular gene transfer, data regarding the kinetics and extent of transgene expression are very limited.

Conclusions.—For the efficient translation of preclinical to clinical vascular gene transfer studies, the kinetics and extent of transgene expression should be determined. Novel imaging technologies and unique clinical scenarios for obtaining tissue should be considered.
Assessment of Epstein-Barr Virus Association With Pediatric Non-Hodgkin Lymphoma in Immunocompetent and in Immunocompromised Patients in Argentina
Authors: Chabay Paola A. , De Matteo Elena N. , Aversa Luis , Maglio Silvana , Grinstein Saúl , Preciado María Victoria
Published: January 2021

Context.—Epstein-Barr virus (EBV) has been classically associated with 3 malignancies, Burkitt lymphoma, B-cell lymphoproliferative syndromes, and nasopharyngeal carcinoma, and more recently with Hodgkin disease, T-cell lymphomas, and gastric and breast carcinomas, as well as with leiomyosarcoma and leiomyoma associated with immunosuppression.

Objective.—To compare EBV expression in Argentine tumor samples with those reported elsewhere, we analyzed EBV expression in an Argentine pediatric population with non-Hodgkin lymphoma and correlated these results with clinical course and outcome.

Methods.—We studied EBV presence by latent membrane protein-1 protein labeling by immunohistochemistry, by in situ hybridization, and by polymerase chain reaction for Epstein-Barr–encoded RNAs (EBERs) in formalin-fixed and paraffin-embedded non-Hodgkin lymphoma tissue samples (collected retrospectively) from 32 pediatric patients at Ricardo Gutiérrez Children's Hospital from 1993 to 2000.

Results.—Eight out of the 32 (25%) non-Hodgkin lymphoma cases showed latent membrane protein-1 and EBERs by in situ hybridization positive staining in tumor cells. Among EBERs and latent membrane protein-1–positive cases, there were 5 immunocompromised patients, with either human immunodeficiency virus infection or primary immunodeficiency. The EBERs in situ hybridization results were confirmed by EBERs polymerase chain reaction in good-quality DNA from 11 samples, with 3 proving positive and 8 negative.

Conclusions.—The association of EBV with non-Hodgkin lymphoma in the Argentine pediatric population was low (25%), and this figure rose to 100% when only the immunocompromised patients subgroup was considered, confirming that the virus is probably a cofactor in the lymphomagenesis of some but not all pediatric non-Hodgkin lymphoma. So far, no differences in clinical outcome are discernible between EBV-positive and EBV-negative non-Hodgkin lymphoma patients.