bluuebunny/crossref_metadata_2025 huggingface dataset:
Freshwater Invertebrates of Southwestern South America: Diversity, Biogeography, and Threats
Authors: Valdovinos Zarges Claudio , Fierro Pablo , Olmos Viviana
Published: February 2021

This chapter reviews the current state of knowledge of invertebrates of rivers, lakes, and wetlands in western South America, from southern Peru to the Strait of Magellan in southern Chile. A characterization of the diverse groups of insects, mollusk crustaceans, and other smaller groups is presented, and a biogeographic analysis of them is made with emphasis on their main forcing factors, ecology, and threats in the Anthropocene. This fauna presents Gondwanic characteristics, with clear North–South latitudinal patterns, covering from the Desert of Atacama in the North, one of the most arid deserts of the world, to the rainy and cold regions of the southern end of South America. The central zone of this territory includes one of the global biodiversity “hot spots,” which currently presents serious threats associated with changes in habitat, introduction of invasive species, climate change, and overexploitation of aquatic resources.
The Potential of Sentinel-2 Satellite Images for Land-Cover/Land-Use and Forest Biomass Estimation: A Review
Authors: Isbaex Crismeire , Margarida Coelho Ana
Published: February 2021

Mapping land-cover/land-use (LCLU) and estimating forest biomass using satellite images is a challenge given the diversity of sensors available and the heterogeneity of forests. Copernicus program served by the Sentinel satellites family and the Google Earth Engine (GEE) platform, both with free and open services accessible to its users, present a good approach for mapping vegetation and estimate forest biomass on a global, regional, or local scale, periodically and in a repeated way. The Sentinel-2 (S2) systematically acquires optical imagery and provides global monitoring data with high spatial resolution (10–60 m) images. Given the novelty of information on the use of S2 data, this chapter presents a review on LCLU maps and forest above-ground biomass (AGB) estimates, in addition to exploring the efficiency of using the GEE platform. The Sentinel data have great potential for studies on LCLU classification and forest biomass estimates. The GEE platform is a promising tool for executing complex workflows of satellite data processing.
Evergreen Oak Biomass Residues for Firewood
Authors: Malico Isabel , Cristina Gonçalves Ana , M.O. Sousa Adélia
Published: February 2021

This chapter presents the assessment of the availability for residential heating of residual biomass from cork and holm oaks in a 12,188 ha agroforest area in Portugal. First, the above-ground biomass of evergreen oaks using very high spatial resolution satellite images was determined, followed by the definition of different scenarios for residues removal from the stands. The useful energy potential of the firewood that can be collected from the study area under the various silviculture scenarios was determined considering different energy conversion technologies: open fireplaces (still popular in Portugal) and more efficient closed burning appliances. Additionally, emissions of airborne pollutants from combusting all the available residual biomass in the study area were determined. Depending on the percentage of residues collected when the trees are pruned and on the conversion technologies used, the energy potential of evergreen oak firewood ranged from 5.0 × 106 MJ year−1 to 7.5 × 107 MJ year−1. Heavier pruning combined with the use of open fireplaces generates less useful heat and much higher emissions of pollutants per unit useful energy produced than lighter pruning combined with a more efficient technology. This case study illustrates the need to promote the transition from inefficient to more efficient and cleaner technologies.
Armed with Cameras and Guns
Authors: Vezub Julio E. , De Oto Alejandro J. , Santiago-Ortiz Aurora ,   Philosophy Documentation Center
Published: February 2021

Vezub and De Oto parse out the double discourses present in anthropological photography in twentieth-century Argentine nationhood. Ethnography thus becomes a powerful tool to create the national archive, reaffirming the coloniality of power, by way of representation and through the placement of indigenous bodies in relation to ethnographers who, engaged in processes of internal colonialism, behaved like earlier colonial explorers. This article presents a rupture in the dominant narrative as it interrupts myths of nationhood and integration of the Tehuelches people with a counternarrative that presents decolonial possibilities within the photographic archive. Maintaining the ambiguity in the discourse of Peronism itself, the authors emphasize that, while financing these ethnographic campaigns, Peronist leaders also supported emancipatory policies for the racialized working class. Los descamisados, a shirtless working-class and subaltern figure, emerges with Peronism, as a positive alternative to suit-wearing oligarchs in discourses of nationhood and nation-building.
Sonerila longipedunculata sp. nov., a new species of Melastomataceae from the southern Western Ghats, India, with additional notes and lectotypification of Sonerila travancorica
Authors: Resmi Sekarathil , Nampy Santhosh
Published: February 2021

A new species of Melastomataceae, Sonerila longipedunculata Resmi & Nampy sp. nov., is described from the southern Western Ghats, India. It is morphologically close to S. travancorica, but differs by the tuberous root stock, fleshy stems, ovate to cordate lamina, longer, angular peduncles, 3-ribbed hypanthium, ovate-elliptic petals, acute anthers, and 3-ribbed capsules. Detailed description, distribution map, and photographic images are provided. The morphological differences with relevant species are discussed. The status of the new species is provisionally assessed here as ‘critically endangered’ according to IUCN Red List Categories and Criteria. The name Sonerila travancorica is lectotypified and its identity is discussed. The status of Sonerila longipetiolata is discussed and is synonymised under S. travancorica.
Meningioma Presenting as an Intraoral Mass in a Patient With Neurofibromatosis Type 1
Authors: Pfeifer John D. , Hill D. Ashley , Ramos Carlos V. , Wippold Franz J. , Dehner Louis P.
Published: February 2021

A 77-year-old woman with neurofibromatosis type 1 presented with ill-fitting dentures due to intraoral extension of a right temporal fossa mass. Computed tomographic scanning demonstrated that the masticator space mass bowed the zygomatic arch and remodeled the lateral orbit and maxillary sinus walls, findings that were consistent with the clinical diagnosis of a neurofibroma with possible malignant transformation. However, light microscopic, immunohistochemical, and ultrastructural examination of tissue from an incisional biopsy specimen were diagnostic of meningioma. This case illustrates that the clinicopathologic differential diagnosis of an enlarging mass in patient with neurofibromatosis should include sporadic, unrelated neoplasms as well as tumors known to be associated with the syndrome.
Multiple Myeloma Involving the Myocardium and Coronary Vessels
Authors: Champeaux Anne L. , Blaser Jason L. , Myers Jerome B. , Schachter David T.
Published: February 2021

We report a case of metastatic plasmacytoma to the myocardium and coronary vessels in a 57-year-old man with multiple myeloma. Originally, the patient had a large plasmacytoma in his left chest wall and lung. He received local radiation and chemotherapy. Subsequently, the patient presented with symptoms of congestive heart failure. He had no prior history of cardiac disease. The patient was treated medically and later died from respiratory failure. At autopsy, a metastatic plamacytoma was indentified within the myocardium and externally compressing the coronary arteries. The tumor infiltrated into the coronary sinus. It is difficult to speculate whether the patient's symptoms were due to cardiac involvement since the tumor burden in his chest was also considerable. To our knowledge, coronary vessel involvement with plasmacytoma has not been previously described.
Molecular Resistance Testing ofHelicobacter pyloriin Gastric Biopsies
Authors: Peña Jeremy Andrew , Fox James G. , Ferraro Mary Jane , Versalovic James
Published: February 2021

Objective.—To evaluate simultaneous diagnosis of infection and molecular resistance testing of Helicobacter pylori.

Methods.—Gastric biopsies were obtained from 26 rapid urease-positive and 51 rapid urease-negative test kits used to diagnose H pylori infection. Following glass bead–assisted DNA isolation, amplification of H pylori 16S ribosomal DNA (rDNA), glmM, and 23S rDNA target genes was performed.

Results.—Helicobacter pylori DNA was successfully amplified from 100% (26/26) of urease-positive and 3.9% (2/51) of urease-negative gastric biopsies. Subsequent restriction enzyme–mediated digestion of 23S rDNA amplification products revealed that 17% (4/24) of urease-positive and H pylori DNA–positive biopsy specimens contained point mutations (A2142G or A2143G) associated with clarithromycin resistance. Helicobacter pylori DNA from gastric biopsies was successfully amplified 8 weeks following rapid urease testing.

Conclusion.—Helicobacter pylori genotyping may be used to detect macrolide-resistant H pylori in individuals prior to initiation of therapy or in patients refractory to anti-H pylori therapy. Two urease-negative specimens yielded Helicobacter DNA distinct from that of H pylori and indicated the need for further investigations of Helicobacter species present in the human stomach.
Adult Polyglucosan Body Disease
Authors: Milde Petra , Guccion John G. , Kelly John , Locatelli Eduardo , Jones Robert V.
Published: February 2021

We describe a case of adult polyglucosan body disease with characteristic clinical symptoms of peripheral neuropathy, upper motor neuron signs, and bowel and bladder dysfunction. Sural nerve biopsy revealed diagnostic intra-axonal polyglucosan bodies. On electron microscopic examination, the inclusions were located mainly within myelinated nerve fibers and consisted of branched filaments that were 6 to 8 nm wide. The diagnosis of adult polyglucosan body disease was confirmed by a skin biopsy from the axilla showing similar inclusions in myoepithelial cells of apocrine glands. This report provides additional evidence that skin biopsy, to date advocated by a single case report only, may be a less invasive and simpler diagnostic alternative to sural nerve or brain biopsies.
Spindle Cell Epithelioma of the Vagina Shows Immunohistochemical Staining Supporting Its Origin From a Primitive/Progenitor Cell Population
Authors: Skelton Henry , Smith Kathleen J.
Published: February 2021

Spindle cell epitheliomas of the vagina (SCEVs) coexpresses epithelial and mesenchymal markers and were first described as a “mixed tumors of the vagina.” However, unlike mixed tumors of other organs, which are believed to originate from myoepithelial cells, SCEVs neither immunohistochemically nor ultrastructurally show features of myoepithelial cells. The present expanded battery of immunohistochemical stains is presented on this rare tumor, including cytokeratin AE1/AE3, CK7, CK20, S100 protein, epithelial membrane antigen, α-smooth muscle actin, desmin, CD34, CD99, Bcl-2, vimentin, estrogen and progesterone receptors, and Ki-67. There was minimal expression of α-smooth muscle actin and negative staining with S100 protein, with coexpression of cytokeratins and vimentin and expression of estrogen and progesterone receptors, as previously reported in SCEVs. In addition, diffuse expression of CD34, CD99, and Bcl-2 immunohistochemical stains was found, which has not previously been reported. The coexpression of CD34, CD99, and Bcl-2 in SCEVs is consistent with its origin from a primitive/progenitor cell population.
Primary Follicular Large Cell Lymphoma of the Testis in a Child
Authors: Lu Di , Medeiros L. Jeffrey , Eskenazi Allen E. , Abruzzo Lynne V.
Published: February 2021

Primary follicular lymphoma of the testis in childhood is extremely rare. To our knowledge, only 5 cases have been reported to date. We report a case in a 6-year-old boy who presented with painless right scrotal enlargement. Right radical orchiectomy revealed a follicular large cell lymphoma with diffuse areas confined to the testis and epididymis, clinical stage IE. Immunohistochemical stains demonstrated that the neoplastic cells were of B-cell lineage, positive for CD10, CD20, CD79a, and BCL-6. Staining for CD21 accentuated networks of dendritic reticulum cells within the nodules. The cells were negative for BCL-2, p53, and T-cell antigens. There was no evidence of the t(14;18) detected by polymerase chain reaction. The data suggest that follicular lymphoma of the testis in children has a different pathogenesis than follicular lymphoma in adults.
Colonic Adenocarcinoma Metastasizing as a Germ Cell Neoplasm
Authors: Petricek C. M.
Published: February 2021

Mixed tumors of the gastrointestinal tract, including both adenocarcinoma and germ cell neoplasm, have been reported infrequently. In the colon, only 9 cases, to our knowledge, have been described in the English-language literature. This is the case of a 29-year-old man with an unsuspected mixed colonic neoplasm that metastasized as the germ cell component.
Routine Syndecan-1 Immunohistochemistry Aids in the Diagnosis of Chronic Endometritis
Authors: Bayer-Garner Ilene B. , Nickell Jennifer A. , Korourian Soheila
Published: February 2021

Context.—Chronic endometritis is reportedly observed in 3% to 10% of women undergoing endometrial biopsy for abnormal uterine bleeding. The diagnosis of chronic endometritis rests on the identification of the plasma cells. Their identification may be obscured by a mononuclear cell infiltrate, plasmacytoid stromal cells, abundant stromal mitoses, a pronounced predecidual reaction in late secretory endometrium, menstrual features, or secondary changes due to exogenous progesterone treatment prior to the biopsy. Syndecan-1 is a proteoglycan that is found on the cell surface of plasma cells and keratinocytes. Immunohistochemistry stains for this antibody may facilitate diagnosis of chronic endometritis.

Objective.—To determine whether or not routine syndecan-1 immunohistochemistry will aid in the diagnosis of chronic endometritis.

Design.—Immunohistochemistry stains for syndecan-1 were performed on 3 levels of 47 endometrial biopsies from patients with abnormal uterine bleeding. None of the patients had endometrial hyperplasia or an underlying malignancy. Clinical correlation and follow-up was attempted in 20 cases that showed evidence of plasma cells by syndecan-1 by immunohistochemistry.

Results.—Plasma cells were identified in 20 cases, 7 of which were initially diagnosed as chronic endometritis. The remaining 13 positive cases were diagnosed as tubal metaplasia (1), secretory endometrium (4), proliferative endometrium (4), menstrual endometrium (1), endometrial polyp (1), secretory endometrium with endometrial polyp (1), and endometrial polyp with exogenous hormone effect (1) based on the original hematoxylin-eosin section.

Conclusions.—Syndecan-1 may be a useful adjunct in the diagnosis of chronic endometritis. Approximately half of the cases of chronic endometritis responded to an antibiotic regime; thus, this diagnosis is important and may potentially obviate the need for surgical intervention.
Applications of Flow Cytometry and Immunohistochemistry to Diagnostic Hematopathology
Authors: Dunphy Cherie H.
Published: February 2021

Objective.—Diagnostic hematopathology depends on the applications of flow cytometric immunophenotyping and immunohistochemical immunophenotyping combined with the cytomorphology and histologic features of each case. Select cases may require additional ancillary cytogenetic and molecular studies for diagnosis. The purpose of this review is to focus on the applications of flow cytometric and immunohistochemical immunophenotyping of paraffin-embedded tissue to diagnostic hematopathology. Advantages and disadvantages of these techniques are examined.

Data Sources.—The literature is extensively reviewed (PubMed 1985–2003) with an emphasis on the most recent applications and those that are most useful clinically, both diagnostically and prognostically.

Study Selection.—Studies were selected based on statistically significant results in large studies with reported adequate clinical follow-up.

Data Extraction.—The methodology was reviewed in the selected studies to ensure reliable comparison of reported data.

Data Synthesis.—Flow cytometric immunophenotyping offers the sensitive detection of antigens for which antibodies may not be available for paraffin immunohistochemical immunophenotyping. However, paraffin immunohistochemical immunophenotyping offers preservation of architecture and evaluation of expression of some proteins, which may not be available by flow cytometric immunophenotyping. These techniques should be used as complimentary tools in diagnostic hematopathology.

Conclusions.—There are extensive applications of flow cytometric and immunohistochemical immunophenotyping to diagnostic hematopathology. As cytogenetic and molecular findings evolve in diagnostic hematopathology, there may be additional applications of flow cytometric and immunohistochemical immunophenotyping to this field of pathology.
Pneumocystis carinii Infection
Authors: Wazir Javed F. , Ansari Naseem A.
Published: February 2021

Objective.—To review and update the literature on current trends with regard to Pneumocystis carinii (jiroveci ) diagnosis, treatment modalities, and its role in human disease processes.

Data Sources.—Bibliographic databases (PubMed and Ovid) were searched for material and data between 1980 and September 2003 relevant to the review. Indexing terms used were “Pneumocystis carinii pneumonia,” and “Pneumocystis jiroveci,” with the English language as a constraint. Other sources were the PhD thesis of one of the authors (J.F.W., London University, 1993) and the library at the Arabian Gulf University in the Kingdom of Bahrain.

Study Selection.—Acquired immunodeficiency syndrome and organ transplant cases with Pneumocystis carinii pneumonia.

Data Extraction.—Independent extraction by 2 observers.

Data Synthesis.—We reviewed the major characteristics of P carinii (jiroveci ) with special emphasis on the more recently acquired data including the presence of a round pore in the cyst wall, which appears to be used for the release of sporozoites, supporting the hypothesis of sexual reproduction in P carinii (jiroveci ).

Conclusions.—Opportunistic infection with P carinii (jiroveci ) remains a significant cause of morbidity and mortality in human immunodeficiency virus and non-human immunodeficiency virus–associated immunosuppressed patients. Diagnosis may be achieved in the majority of cases by routine cytochemical stains and specialized techniques such as immunocytochemistry and polymerase chain reaction. The incidence of P carinii pneumonia can significantly be reduced with effective use of prophylaxis and early detection of cases at high risk. Immunization for P carinii pneumonia is in the early stages and presents a challenging area for research.
A Hydatidiform Mole in a Postmenopausal Woman
Authors: Garcia Monica , Romaguera Rita L. , Gomez-Fernandez Carmen
Published: February 2021

Gestational trophoblastic disease occurs in less than 1 per 1200 pregnancies in the United States. The spectrum of this disease ranges from benign hydatidiform mole to trophoblastic malignancy (placental-site trophoblastic tumor and choriocarcinoma). Benign gestational trophoblastic disease generally occurs in women of reproductive age and is extremely rare in postmenopausal women. To our knowledge, our case represents only the third description in the world literature of a benign complete hydatidiform mole in a woman with a history of amenorrhea greater than 1 year. We describe the case of a 61-year-old postmenopausal woman who underwent an emergent total abdominal hysterectomy due to uncontrollable vaginal bleeding associated with an increased serum β-human chorionic gonadotropin level. The resected uterus contained an endometrial, cystic, grapelike tumor. Microscopic examination demonstrated hydropic degenerated villi with a circumferential trophoblastic cell proliferation and moderate atypia, consistent with a complete hydatidiform mole. The morphologic and immunophenotypic characteristics are presented, as well as the results of a literature review.
Basaloid Squamous Cell Carcinoma of the Esophagus With or Without Adenoid Cystic Features
Authors: Li Tie-Jun , Zhang Yong-Xin , Wen Julie , Cowan Daniel F. , Hart John , Xiao Shu-Yuan
Published: February 2021

Context.—Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare malignant tumor that morphologically could bear some resemblance to adenoid cystic carcinoma (ACC) originating from salivary glands.

Objective.—The purpose of this study is to describe the histologic, immunohistochemical, and ultrastructural findings of BSCCs of the esophagus, with an emphasis on comparing tumors with or without adenoid cystic features.

Design.—We reviewed 239 cases of primary esophageal carcinoma and detected 12 cases (5%) of BSCC. The light and electron microscopic findings and immunocytochemical localization of various antigens, including cytokeratins (AE1, AE3), carcinoembryonic antigen, epithelial membrane antigen, S100, smooth muscle actin, and p53, were examined in these BSCC cases.

Results.—Histologically, all BSCCs were composed of solid lobules or nests of basaloid cells with well-demarcated outlines surrounded by a fibrous stroma. Seven of 12 tumors showed areas of ACC-like features, that is, cribriform-like pseudoglandular lumina formation and hyaline material surrounding the tumor nests, whereas the remaining 5 tumors were apparently pure basaloid carcinomas. These 2 groups of tumors were histologically and immunohistochemically identical in many aspects, namely, high-grade nuclei of the tumor cells with frequent mitoses, abundant comedo-type necrosis, focal areas of concomitant squamous differentiation, consistent immunoreactivity for cytokeratins, and poor or absent staining for S100 and smooth muscle actin. Ultrastructurally, the basaloid tumor cells exhibited relatively undifferentiated cellular characteristics and undeveloped cell organelles.

Conclusion.—Basaloid squamous cell carcinomas of the esophagus frequently have an intimate association with ACC-like patterns, but their histologic, immunocytochemical, and ultrastructural features correspond more to poorly differentiated squamous cell carcinoma than to salivary gland ACC. This distinction is important because genuine ACC is much less aggressive than BSCC.
William H. Welch, MD, and the Discovery ofBacillus welchii
Authors: Lucey Brendan P. , Hutchins Grover M.
Published: February 2021

William H. Welch, MD, and his colleagues performed an autopsy at The Johns Hopkins Hospital in October 1891 on a 38-year-old man and discovered a new bacterium, Bacillus aerogenes capsulatus. During the postmortem examination, gas bubbles were noted within many of the patient's blood vessels. Welch's laboratory personnel determined that a previously unknown bacterium was the source of the gas. Through a series of experiments, the organism's characteristics were described and its pathophysiology was detailed, findings that proved accurate in explaining gas gangrene during World War I. Welch never followed up these initial investigations with more experimentation. His subsequent writings regarding the bacterium that came to be known, appropriately, as Bacillus welchii consisted mostly of case reports from other medical institutions and summaries of previous data.
Renal Tumor With Overlapping Distal Nephron Morphology and Karyotype
Authors: Lindgren Valerie , Paner Gladell P. , Flanigan Robert C. , Clark Joseph I. , Campbell Steven C. , Picken Maria M.
Published: February 2021

Although most renal epithelial tumors are derived from the proximal nephron, approximately 10% are believed to originate in the distal nephron. This latter group encompasses oncocytoma, chromophobe renal cell carcinoma, and several rare types, including collecting duct carcinoma and renal medullary carcinoma. Despite progress in the classification of renal tumors, a small subset of renal carcinomas remains unclassified (ie, renal cell carcinoma, not otherwise specified). We describe a metastatic tumor consisting of cells with overlapping distal nephron morphologies, including foci of oncocytoma, chromophobe renal cell carcinoma, and collecting duct carcinoma, as well as sarcomatoid dedifferentiation. Special stains were inconclusive, and ultrastructural study demonstrated abundant mitochondria and no microvesicles. The karyotype was hypodiploid with 41 chromosomes and abnormalities reported in all 3 phenotypes present. Rearrangements of 1p and of 11q13 previously seen in divergent subsets of oncocytomas were concomitantly present in the current tumor. Thus, this malignancy has features consistent with distal nephron derivation and demonstrates the convergence of the varied tumor morphologies arising within this site. Furthermore, this case exemplifies the value of cytogenetic analysis in the characterization of renal cell carcinoma, not otherwise specified. In view of recent advances in treatment approach, especially for collecting duct carcinoma, further categorization of this nondescript and heterogeneous group of renal cell carcinomas, not otherwise specified, at least by its derivation in relationship to the renal nephron (distal vs proximal), may be of value in the choice of treatment modality.
Primary Combined Squamous and Small Cell Carcinoma of the Larynx: A Case Report and Review of the Literature
Authors: Jaiswal Vilkesh R. , Hoang Mai P.
Published: February 2021

Primary laryngeal carcinomas comprise approximately 2% to 5% of all malignancies worldwide. Of these laryngeal carcinomas, approximately 99% are primary squamous cell carcinomas. During the past 30 years, about 160 cases of primary small cell carcinoma of the larynx have been reported. Combined primary squamous and small cell carcinoma of the larynx, the so-called composite tumor of the larynx, is even more rare, with only 13 published cases to date. Although the major risk factors for developing these composite tumors of the larynx are thought to be similar to other more common neoplasms of the larynx, such as squamous cell carcinoma, the treatment and prognosis are different. We report an additional case of combined small cell carcinoma of the larynx and discuss the histogenesis of this unusual neoplasm.
Peliosis Hepatis Associated With Lymphoplasmacytic Lymphoma: An Autopsy Case Report
Authors: Corpa Marcus V. N. , Bacchi Maura M. , Bacchi Carlos E. , Coelho Kunie I. R.
Published: February 2021

A 72-year-old man with no previous history of liver disease was admitted to our university hospital with severe dyspnea, edema of the lower limbs, and weight loss. Within a few days of hospitalization, he died due to severe bleeding in the upper digestive tract. At autopsy, the liver displayed typical gross features of peliosis hepatis. In addition, a diffuse infiltration of liver, spleen, bone marrow, and lymph nodes by lymphoplasmacytic lymphoma was disclosed by light microscopy. In the liver, the neoplastic cells partially filled the peliotic cavities. Peliosis hepatis is a rare liver disease characterized by multiple blood-filled, dilated cavities within the liver parenchyma. Association of lymphoplasmacytic lymphoma and peliosis hepatis has rarely been reported in the literature. The pathologic findings of such an unusual association and a review of the literature are presented.
The -omics Era and Its Impact
Authors: Kiechle Frederick L. , Zhang Xinbo , Holland-Staley Carol A.
Published: February 2021

Objective.—To review the advances in clinically useful molecular biologic techniques and to identify their applications, as presented at the 12th Annual William Beaumont Hospital DNA Symposium.

Data Sources.—The 7 manuscripts submitted were reviewed and their major findings were compared with literature on the same or related topics.

Study Selection.—Manuscripts address the use of molecular techniques in the detection of severe acute respiratory syndrome (SARS) and bacterial ribosome mutations, which may lead to ribosome-targeted drug resistance; pharmacogenomics as a clinical laboratory service and example of warfarin dosing using CYP2C9 mutation analysis; definition of the potential of cytosine arabinoside incorporation into DNA to disrupt transcription using an in vitro model of oligonucleotides; use of laser capture microdissection to isolate solid tumor cells free of nontumor cells; and molecular methods used to classify lymphomas.

Data Synthesis.—Two current issues related to the use of molecular tests in the clinical laboratories are (1) decentralization of molecular-based testing to a variety of nonmolecular laboratories and (2) need for wider acceptance of molecular-based testing through its incorporation in clinical practice guidelines. Molecular methods have had a major impact on infectious disease through the rapid identification of new infectious agents, SARS, and the characterization of drug resistance. Pharmacogenomics identifies the genetic basis for heritable and interindividual variation in response to drugs. The incorporation of the nucleoside analog, cytosine arabinoside, into DNA leads to local perturbation of DNA structure and reduces the ability of transcription factors to bind to their specific DNA binding elements as measured by electrophoretic mobility shift assays. Laser capture microdissection of tumor cells can provide an adequate number of cells for whole genome amplification. Gene expression microassay profiles of various lymphomas have modified classification systems and predict prognosis and response to therapy.

Conclusions.—The current -omics era will continue to emphasize the use of microarrays and database software for genomic, transcriptomic, and proteomic screening to search for a useful clinical assay. The number of molecular pathologic techniques will expand as additional disease-associated mutations are defined.
Effect of Polymorphisms in the Cytochrome P450 CYP2C9 Gene on Warfarin Anticoagulation
Authors: Adcock Dorothy M. , Koftan Charles , Crisan Domnita , Kiechle Frederick L.
Published: February 2021

Context.—Warfarin is a widely used anticoagulant with efficacy in treatment and prevention of thrombosis. Patient management, however, is difficult because of interindividual variation in response to standard doses due to significant differences in metabolic rates. Warfarin metabolism is under genetic control, involving primarily the CYP2C9 gene encoding the enzyme that catalyzes the conversion of warfarin to inactive metabolites.

Objective.—Several polymorphisms of CYP2C9 have been reported; the variant alleles *2 and *3 have decreased enzymatic activity. The objective of this case study is to investigate the relationship between CYP2C9 genotype and warfarin anticoagulation.

Design.—A case of deep vein thrombosis treated with the standard warfarin dose is investigated for intensity of anticoagulation and CYP2C9 genotype; the case illustrates the relationship between CYP2C9 variant and overanticoagulation with subsequent bleeding complication.

Results.—The patient's genotype, CYP2C9*1*3, correlated with an exaggerated anticoagulant response during the initiation of warfarin therapy at standard dose, and a bleeding episode ensued. Based on heterozygosity for the *3 variant allele, it was recommended that the patient be maintained on a low-dose warfarin regimen.

Conclusions.—The practical implications of identifying genetic risk factors that lead to overanticoagulation are multiple. Genotype knowledge of the CYP2C9 variant alleles may help the clinician to individualize warfarin therapy with the ultimate goals of shortening the initial period of induction therapy, reaching a stable maintenance dose earlier, and minimizing bleeding complications in patients who are high responders and need lower warfarin doses.
Salivary Adenocarcinoma, Not Otherwise Specified: A Collection of Orphans
Authors: Li Jiang , Yiyao Wang Beverly , Nelson Magalie , Li Lei , Hu Yuhua , Urken Mark L. , Brandwein-Gensler Margaret
Published: February 2021

Context.—Salivary adenocarcinoma, not otherwise specified, refers to gland-forming malignancies that do not satisfy the diagnostic requirements of other “named” malignancies.

Objective.—To review the features of 11 patients with salivary adenocarcinoma, not otherwise specified. To also compare the diagnostic frequencies of 2 databases, one from the Mount Sinai Medical Center (New York, NY), the other from the Shanghai Ninth People's Hospital (Shanghai, People's Republic of China).

Design.—Pathology files were searched to establish a database of salivary tumors. All available hematoxylin-eosin– stained slides from the resection specimens diagnosed as either adenocarcinoma, not otherwise specified, or with vague or unusual diagnoses (eg, probable carcinoma-ex-pleomorphic adenoma) were pulled from our files and reexamined. Dates of death were confirmed with the Social Security Death Index.

Results.—We identified 11 patients with salivary adenocarcinoma, not otherwise specified, ranging in age from 49 to 80 years (median, 67 years), with a male preponderance. The parotid gland was the most common site of tumor origin. Ten of these tumors were high grade, and 1 was intermediate grade. Two patients were diagnosed at stage II, while the remaining patients were diagnosed at stage III or IV. Histologically, all tumors were invasive, with variable glandular differentiation and diverse architectural patterns. The diverse cytologic tumor cell types included cuboidal, columnar, epithelioid, polygonal, oncocytoid, clear, melanoma-like, mucinous, sebaceous, and plasmacytoid. Four patients died after 4 to 27 months (mean, 15 months), 1 patient is alive with disease at 12 months, 1 patient is disease-free at 14 years, and 3 patients remain disease-free after short follow-ups (10, 12, and 12 months). One patient had surgery just recently, and the remaining patient had no follow-up.

Conclusions.—Salivary adenocarcinoma, not otherwise specified, is an aggressive, high-grade malignancy, with a predisposition for the parotid gland. It is characterized by cytologic and architectural diversity and an invasive growth pattern.
Cystic Nephroma: A Histologic and Immunohistochemical Study of 10 Cases
Authors: Mukhopadhyay Sanjay , Valente Alfredo Luis , de la Roza Gustavo
Published: February 2021

Context.—Cystic nephroma is a rare and controversial benign multicystic renal tumor. While the clinical, radiologic, and histologic features of cystic nephroma are well described, the immunohistochemical features are not. The role of immunohistochemistry in the differential diagnosis, which includes multicystic renal cell carcinoma, is also unknown.

Objective.—To define the histologic and immunohistochemical features of cystic nephroma.

Design.—Ten cases of cystic nephroma diagnosed at 2 institutions during a period of 10 years were stained with an immunohistochemical panel consisting of 20 immunostains.

Results.—Median age at diagnosis was 61 years, with a range from 31 to 79 years. The female-to-male ratio was 9:1. Grossly, the tumors were multicystic masses without solid nodules. Histologic features included cysts lined by flat, cuboidal, or hobnail epithelium and septa variably lined by fibrous (10/10 cases) and/or ovarian-like (7/10 cases) stroma. Corpus albicans–like acellular hyalinized structures were noted in the septa in 9 of 10 cases. The cyst epithelium showed consistent positivity for distal tubule/collecting duct markers (cytokeratin 19, cytokeratin AE1/AE3, epithelial membrane antigen) and variable positivity for proximal tubule markers (α1-antitrypsin, lysozyme, CD15, CD10). The ovarian-like stroma (present in 7/10 cases) stained positively for progesterone receptors (6/7 cases) and estrogen receptors (4/7 cases).

Conclusions.—Our immunohistochemical findings confirm a previous report of both distal tubule/collecting duct and proximal tubule differentiation in cystic nephroma. Stromal estrogen and/or progesterone receptor positivity in the majority of cases of cystic nephroma is a novel finding.
Idiopathic Bilateral Auricular Ossificans: A Case Report and Review of the Literature
Authors: High Whitney A. , Larson Matthew J. , Hoang Mai P.
Published: February 2021

Petrification of the auricle results in a rigid and immalleable ear. The etiology of such a finding is usually ectopic calcification. The condition has been associated with injurious processes, such as cold injury, and with various endocrinopathies, including Addison disease. In a significant number of cases, ossification occurs without knowledge of the precipitating cause or event. True auricular ossification is a rare occurrence, with only 12 histologically confirmed cases in the literature. We herein present the clinical and pathologic findings of another case. A 60-year-old man with diet-controlled diabetes presented with a 10-year history of slowly and insidiously stiffened auricles. He denied any precipitating historical events. Routine testing did not demonstrate systemic abnormalities. Radiographic examination revealed opacities consistent with bony structure in the auricles of the ears, with the right more prominent than the left. Histologic sampling demonstrated ossification with deposition of trabecular bone in proximity to normal elastic cartilage.
Gastrointestinal Stromal Tumor Presenting as a Recurrent Vaginal Mass
Authors: Ceballos Katherine M. , Francis Julie-Ann , Mazurka John L.
Published: February 2021

Gastrointestinal stromal tumors are CD117 (c-Kit)–positive mesenchymal neoplasms with histologic and ultrastructural features of the interstitial cell of Cajal. While tumors outside of the gastrointestinal tract have been described, to our knowledge the case we present is the first such case in the vagina. We describe a 75-year-old woman with a recurrent vaginal gastrointestinal stromal tumor without apparent rectal involvement. This tumor was characterized by short intersecting fascicles of spindled cells, focal necrosis, and 12 to 15 mitoses per 50 high-power fields. Immunohistochemistry revealed diffuse cytoplasmic positivity for CD117 (c-Kit), CD34, vimentin, and h-caldesmon. Tumor cells were negative for S100, desmin, actin, and CAM 5.2. The differential diagnosis in this case included a vaginal smooth muscle tumor. While histologically similar to a smooth muscle neoplasm, the immunohistochemical profile ruled out smooth muscle differentiation. Gastrointestinal stromal tumor should be considered in the differential diagnosis of vaginal mesenchymal neoplasms.
Leukemoid Reaction: A Diagnostic Clue in Metastatic Carcinoma Mimicking Classic Hodgkin Lymphoma
Authors: Mukhopadhyay Sanjay , Mukhopadhyay Surabhi , Banki Katalin , Mahajan Shirish
Published: February 2021

We report on 2 patients who were initially suspected to have classic Hodgkin lymphoma because of lymphadenopathy and the presence of Reed-Sternberg–like cells. Both patients had an associated leukemoid reaction (using a threshold leukocyte count of 50 000/μL) and were eventually diagnosed with metastatic carcinoma. Disseminated carcinoma can mimic Hodgkin lymphoma clinically, radiologically, and histologically. Reed-Sternberg–like cells may be found in carcinomas, and they represent a particularly challenging diagnostic pitfall for the unwary. When these cells lead to a suspicion of Hodgkin lymphoma, the presence of a leukemoid reaction should prompt the pathologist to question the diagnosis. Misdiagnosis can be avoided by the use of cytokeratin whenever a leukemoid reaction is present in a suspected case of Hodgkin lymphoma.
Fibrolamellar Hepatocellular Carcinoma Occurring 5 Years After Hepatocellular Adenoma in a 14-Year-Old Girl: A Case Report With Comparative Genomic Hybridization Analysis
Authors: Terracciano Luigi Maria , Tornillo Luigi , Avoledo Pierino , von Schweinitz Dietrich , Kühne Thomas , Bruder Elisabeth
Published: February 2021

An unusual case of fibrolamellar carcinoma of the liver developed 5 years after removal of a hepatocellular adenoma in a 14-year-old girl belonging to a family with Carney syndrome. Both tumors were studied by light and electron microscopy, flow cytometry, and comparative genomic hybridization. The first tumor, removed at the age of 9, was a bulky well-circumscribed liver mass composed of large eosinophilic cells with a focal pseudoglandular pattern but without cytologic atypia or sclerosis. A diagnosis of hepatocellular adenoma was rendered. Five years later, another hepatic tumor was removed from the right lobe. Microscopic examination revealed polygonal cells, each with a large amount of eosinophilic cytoplasm and a round nucleus with a conspicuous nucleolus. These cells were arranged in nests and strands and separated by bands of dense fibrous tissue, leading to a diagnosis of fibrolamellar carcinoma. Comparative genomic hybridization analysis revealed no genetic alteration in the adenoma; however, several chromosomal aberrations (loss of chromosome regions 1p and 4p and gains of chromosome regions 6q, 13q, and Xq) were detected in the fibrolamellar carcinoma. To our knowledge, this is the first report of an association between hepatocellular adenoma and fibrolamellar carcinoma.
Collagenous Gastritis: An Unusual Association With Profound Weight Loss
Authors: Wang Hanlin L. , Shah Amit G. , Yerian Lisa M. , Cohen Russell D. , Hart John
Published: February 2021

Collagenous gastritis is a distinctive disorder characterized by thickening of the subepithelial collagen layer in the gastric mucosa. Although this entity was recognized in 1989, its etiology, pathogenesis, and clinicopathologic features remain poorly understood because of its rarity. An unusual case of collagenous gastritis was observed in a 37-year-old man who presented with profound weight loss, a feature that has not previously been emphasized.
Molecular Analysis to Demonstrate That Odontogenic Keratocysts Are Neoplastic
Authors: Agaram Narasimhan P. , Collins Bobby M. , Barnes Leon , Lomago Deren , Aldeeb Dalal , Swalsky Patricia , Finkelstein Sydney , Hunt Jennifer L.
Published: February 2021

Context.—Odontogenic keratocysts (OKCs) are unique odontogenic lesions that have the potential to behave aggressively, that can recur, and that can be associated with the nevoid basal cell carcinoma syndrome. Whether they are developmental or neoplastic continues to be debated.

Objectives.—To identify loss of heterozygosity of tumor suppressor genes in OKCs and to suggest a pathogenetic origin for these lesions.

Design.—We examined 10 OKCs for loss of heterozygosity of tumor suppressor genes, using a microdissection and semiquantitative genotyping analysis. The genes analyzed included 10 common tumor suppressor genes, as well as the PTCH gene, which is mutated in nevoid basal cell carcinoma syndrome.

Results.—Loss of heterozygosity was seen in 7 of 10 cases, with a frequency between 11% and 80% of the genes studied. The genes that exhibited the most frequent allelic losses were p16, p53, PTCH, and MCC (75%, 66%, 60%, and 60%, respectively). Daughter cysts were associated with a higher frequency of allelic loss (P = .02), but epithelial budding was not.

Conclusions.—Our study indicates that a significant number of OKCs show clonal loss of heterozygosity of common tumor suppressor genes. The finding of clonal deletion mutations of genomic DNA in these cysts supports the hypothesis that they are neoplastic rather than developmental in origin.
Comorbidity in Dementia
Authors: Fu Catherina , Chute Dennis J. , Farag Emad S. , Garakian Justine , Cummings Jeffrey L. , Vinters Harry V.
Published: February 2021

Context.—There is a paucity of accurate postmortem data pertinent to comorbid medical conditions in patients with dementia, including Alzheimer disease.

Objectives.—The purposes of this study were (a) to examine general autopsy findings in patients with a dementia syndrome and (b) to establish patterns of central nervous system comorbidity in these patients.

Design.—Review of autopsy reports and selected case material from 202 demented patients who had “brain-only” autopsies during a 17-year period (1984–2000) and from 52 demented patients who had general autopsies during a 6-year period (1995–2000).

Setting.—Large academic medical center performing approximately 200 autopsies per year.

Results.—Among the 52 patients who underwent complete autopsy, the most common cause of death was bronchopneumonia, which was found in 24 cases (46.1%). Other respiratory problems included emphysema, found in 19 (36.5%) of 52 patients, and pulmonary thromboembolism, found in 9 (17.3%) of 52 patients. In 6 cases, pulmonary thromboembolism was the proximate cause of death. Twenty-one (40.3%) of the 52 patients had evidence of a myocardial infarct (varying ages) and 38 (73.1%) had atherosclerotic cardiovascular disease, 27 of a moderate to severe degree. Four clinically unsuspected malignancies were found: 1 each of glioblastoma multiforme, diffusely infiltrative central nervous system lymphoma, pancreatic adenocarcinoma, and adenocarcinoma of the lung. One patient with frontotemporal dementia and amyotrophic lateral sclerosis died of severe meningoencephalitis/ventriculitis, probably secondary to seeding of the central nervous system by an infected cardiac valve. Of the 202 demented patients who underwent brain-only autopsies, the following types of dementia were found: 129 (63.8%) cases showed changes of severe Alzheimer disease, 21 (10.4%) showed combined neuropathologic abnormalities (Alzheimer disease plus another type of lesion, such as significant ischemic infarcts or diffuse Lewy body disease), 12 (5.9%) cases of relatively pure ischemic vascular dementia, 13 (6.4%) cases of diffuse Lewy body disease, and 8 (4.0%) cases of frontotemporal dementia. The remaining 19 (9.4%) patients showed miscellaneous neuropathologic diagnoses, including normal pressure hydrocephalus and progressive supranuclear palsy. Among the demented patients, 92 (45.5%) had cerebral atherosclerosis, which was moderate to severe in 65 patients (32.2%).

Conclusions.—Some of the conditions found at autopsy, had they been known antemortem, would likely have affected clinical management of the patients. Autopsy findings may be used as a quality-of-care measure in patients who have been hospitalized in chronic care facilities for a neurodegenerative disorder.