bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy Production from Forest Biomass: An Overview
Authors: Cristina Gonçalves Ana , Malico Isabel , M.O. Sousa Adélia
Published: February 2021

As long as care is taken regarding stand and forest sustainability, forest biomass is an interesting alternative to fossil fuels because of its historical use as an energy source, its relative abundance and availability worldwide, and the fact that it is carbon-neutral. This study encompasses the revision of the state of the sources of forest biomass for energy and their estimation, the impacts on forests of biomass removal, the current demand and use of forest biomass for energy, and the most used energy conversion technologies. Forests can provide large amounts of biomass that can be used for energy. However, as the resources are limited, the increasing demand for biomass brings about management challenges. Stand structure is determinant for the amount of residues produced. Biomass can be estimated with high accuracy using both forest inventory and remote sensing. Yet, remote sensing enables biomass estimation and monitoring in shorter time periods. Different bioenergy uses and conversion technologies are characterized by different efficiencies, which should be a factor to consider in the choice of the best suited technology. Carefully analyzing the different options in terms of available conversion technologies, end-uses, costs, environmental benefits, and alternative energy vectors is of utmost importance.
The Influence of Sagittal Plane Spine Alignment on Neurophysiology and Sensorimotor Control Measures: Optimization of Function through Structural Correction
Authors: A. Oakley Paul , M. Moustafa Ibrahim , E. Harrison Deed
Published: February 2021

Increasingly, there is more attention being directed to the role that full spine sagittal alignment plays in causing or exacerbating a variety of musculoskeletal disorders. Similarly, spinal displacements, termed subluxation, are thought to cause dysfunctions in the entire neuromusculoskeletal system that may lead to altered neurophysiological function, abnormal sensorimotor control, and altered autonomic nervous system function. Abnormalities in neutral upright spine alignment (sagittal translation or flexion deformities) are known to increase mechanical loads (stresses and strains) on the central nervous system. These increased mechanical loads may subtly or overtly impair neurophysiological function as measured with evoked potentials in terms of latency and amplitudes of potentials. Proprioceptive afferentation from spine ligaments, muscles and discs are considered a major component of sensorimotor control. The voluminous mechanoreceptors in spinal muscles, ligaments, and discs plays an intimate role, providing the necessary neurophysiological input in a feed forward and feedback system for sensorimotor control via connections to the vestibular, visual and central nervous systems. Of particular interest, a network of neurophysiological connections between spine mechanoreceptors and the sympathetic nervous system has been documented. This chapter explores the hypothesis and evidence that restoring normal posture and spine alignment has important influences on neurophysiology, sensorimotor control and autonomic nervous system functionality. There is limited but high-quality research identifying that sagittal spine alignment restoration plays an important role in improving neurophysiology, sensorimotor control, and autonomic nervous system function. Accordingly, in the current chapter, we review this work in hopes of stimulating further investigations into structural rehabilitation of the spine and posture.
Comparative Genomic Analyses of Primary Effusion Lymphoma
Authors: Mullaney B. P. , Ng V. L. , Herndier B. G. , McGrath M. S. , Pallavicini M. G.
Published: February 2021

Background.—A rare subset of human immunodeficiency virus (HIV) lymphomas, known as primary effusion lymphomas (PELs), are high-grade tumors carrying human herpes virus 8. Mechanisms postulated to contribute to lymphomagenesis include impaired immune surveillance, alterations in hemopoietic regulatory pathways due to expressed viral genes, and acquisition of genomic alterations in regions of the genome that contain regulatory genes. In PEL, limited information exists about the nature of genome-wide aberrations in these rare lymphomas.

Methods.—We used comparative genomic hybridization to detect regions of sequence gain and loss throughout the genome of 8 PEL cases. Regions of DNA sequence loss or gain were confirmed using forward and reverse hybridization and t-statistic analyses.

Results.—Genomic aberrations were identified in 6 of 8 cases, including recurrent gain of sequence in chromosomes 12 [ish enh (12q22;12q23, 12q12;12q23)] in 3 of 8 cases and X [ish enh (X, Xp)] in 2 of 8 cases.

Conclusions.—DNA copy number changes occurred in a majority of PEL cases and are consistent with changes observed in other HIV lymphomas. These observations suggest that common genetic events may occur in HIV-associated lymphoid malignancies, but they probably do not contribute to the unique markers and morphology of PEL. Although individual genetic loci have been evaluated previously in a few PEL cases, to our knowledge this study represents the first reported genome-wide scan of copy number changes in these rare HIV-associated tumors.
Malignant Peripheral Nerve Sheath Tumor With a t(X;18)
Authors: Vang Russell , Biddle David A. , Harrison Wilbur R. , Heck Kent , Cooley Linda D.
Published: February 2021

We describe an ankle tumor arising in a 16-year-old girl. The tumor demonstrated histology typical of a malignant peripheral nerve sheath tumor (MPNST), but exhibited a variant form of the (X;18) translocation associated with synovial sarcoma. Immunohistochemical stains were positive for vimentin, CD57, collagen type IV, and Bcl-2. Routine and molecular cytogenetic studies showed an unbalanced 3-way chromosomal translocation that involved chromosomes X, 18, and 1. Electron microscopic findings were noncontributory. This unusual tumor raises the following questions and possibilities: (1) As the t(X;18) suggests, could this tumor be a monophasic synovial sarcoma with the histologic features of an MPNST? (2) Or, as the histology suggests, is this tumor an MPNST that has a t(X;18)? (3) Finally, could MPNST histology, a t(X;18), and no defining immunohistochemical or electron microscopic features represent an as yet unrecognized part of a spectrum that spans from synovial sarcoma to MPNST or other spindle cell tumors?
Carcinomas of Sweat Glands
Authors: Urso Carmelo , Bondi Roberto , Paglierani Milena , Salvadori Adriana , Anichini Chiara , Giannini Augusto
Published: February 2021

Context.—Several aspects of sweat gland carcinomas (incidence, classification, diagnosis, and behavior) have not been definitively clarified and need to be studied further.

Objective.—The clinicopathologic findings of a large series of sweat gland carcinomas, collected during a period of 15 years, are presented.

Methods.—Sixty sweat gland carcinomas (41 porocarcinomas, 3 syringomatous carcinomas, 8 ductal carcinomas, 5 adenoid cystic carcinomas, and 3 mucinous carcinomas) were analyzed histologically and immunohistochemically.

Results.—Porocarcinomas were composed of eosinophilic and clear atypical cells arranged in solid-cystic lobular masses. These tumors were divided into 2 subgroups: horizontal porocarcinomas, showing a prominent intraepidermal component, and nodular porocarcinomas, which demonstrated predominant nodular growth. Syringomatous carcinomas presented keratinizing and nonkeratinizing cysts, dilated tubules (sometimes with a “tadpole” appearance), small neoplastic ducts, solid islands, and cellular cords. Ductal carcinomas were characterized by a prominent formation of tubules, solid islands, and cellular cords. Adenoid cystic carcinomas presented a characteristic pattern, showing basaloid monomorphous cells with moderately atypical nuclei, arranged in cribriform or solid islands and in tubular structures. Mucinous carcinomas were composed of moderately atypical cells with eosinophilic vacuolated cytoplasm, forming solid and cystic islands floating in large mucin pools. Immunohistochemically, cytokeratin was found in neoplastic cells in all cases, carcinoembryonic antigen was detected in 73% of cases, and actin-positive (myoepithelial) cells were not found.

Conclusions.—Although numerous studies have been published in recent years, the histologic features, histogenesis, and classification of sweat gland carcinomas still remain controversial and need to be clarified by further studies.
Intrasellar Pituicytoma in a Patient With Other Endocrine Neoplasms
Authors: Schultz Alice B. , Brat Daniel J. , Oyesiku Nelson M. , Hunter Stephen B.
Published: February 2021

Considered a neoplasm of pituicytes, pituicytoma is a rare and distinct type of glioma that arises in the suprasellar space and within the sella turcica. Only 12 previously reported cases of pituicytoma are documented in the literature. We report an intrasellar pituicytoma in a 66-year-old man presenting with symptoms and radiologic appearance indistinguishable from a nonfunctional pituitary adenoma. The patient also had a medical history significant for parathyroid adenomas and follicular carcinoma of the thyroid. The intrasellar tumor had morphologic features of a pituicytoma, with interlacing fascicles and a storiform pattern much like a benign fibrous histiocytoma. Immunoreactivity for S100 was strong, but the tumor lacked intercellular collagen type IV. The differential diagnosis of a low-grade spindle cell lesion of the sellar space is discussed, and the literature is reviewed. A summary of the clinical and pathologic features of this case, as well as the 12 previously reported cases, is presented.
Cutaneous Angiosarcoma Complicating Morbid Obesity
Authors: Azam Muhammad , Saboorian M. Hossein , Bieligk Samuel , Smith Todd , Molberg Kyle
Published: February 2021

Herein, we report a case of cutaneous angiosarcoma in a 35-year-old, morbidly obese woman. The tumor arose in the most dependent portion of the lower abdominal panniculus and showed typical changes of chronic lymphedema. The patient underwent a radical resection of her lower abdominal wall panniculus, which showed a multicentric, high-grade angiosarcoma with bilateral superficial inguinal lymph node metastases. Histologically, conventional vasoformative areas were admixed with poorly differentiated sheets of spindle and epithelioid cells. Factor VIII was focally positive (membranous), whereas CD31 showed robust, diffuse positivity (membranous and cytoplasmic). The initial margins of resection were negative, and no follow-up radiation or chemotherapy was given. Following a recurrence at the previous excision site, the patient died 7 months after the surgery. Postmortem examination revealed a widely metastatic tumor that involved multiple organ systems. We believe this is the second report of cutaneous angiosarcoma occurring in a chronically lymphedematous abdominal panniculus due to morbid obesity.
Nodular Histiocytic Hyperplasia of the Endometrium
Authors: Fukunaga Masaharu , Iwaki Satoko
Published: February 2021

A case of nodular histiocytic hyperplasia of the endometrium is described. A 45-year-old Japanese woman was found to have an enlarged uterus during her annual checkup. Hysterectomy and bilateral salpingo-oophorectomy specimens revealed uterine leiomyomas, adenomyosis, and acute salpingitis. A 5-mm, well-demarcated, elevated endometrial nodule (an incidental finding) was present and consisted of round or polygonal histiocytic cells with eccentric nuclei and pale or granular cytoplasm. The nuclei were ovoid, reniform, or crescent-shaped and had fine chromatin and inconspicuous nucleoli, and the cytoplasm contained single or multiple vacuoles. Immunohistochemically, the histiocytic cells were positive for vimentin, CD68, and lysozyme and were negative for cytokeratin, S100 protein, estrogen and progesterone receptors, and CD10. Nodular histiocytic hyperplasia in the endometrium is considered to be a reactive process. Differentiation from neoplasms, including signet-ring cell carcinoma, in curettage specimens is critical to avoid unnecessary surgical resection.
An Isolated Vertebral Metastasis of Urachal Adenocarcinoma
Authors: Taylor Sophia , Bacchini Patrizia , Bertoni Franco
Published: February 2021

We describe a case of urachal adenocarcinoma arising in a 30-year-old woman. The patient underwent partial cystectomy. Three years later, she presented with an isolated metastasis to a thoracic vertebra, which was treated by vertebral corporectomy. Histologic findings are described, and the clinical findings, management, and metastatic patterns of this rare tumor, as well as the differential diagnosis on a biopsy specimen, are discussed.
Immunohistochemical Expression of Matrix Metalloproteinases 1, 2, 9, and 14 in Dermatofibrosarcoma Protuberans and Common Fibrous Histiocytoma (Dermatofibroma)
Authors: Weinrach David M. , Wang Kim L. , Wiley Elizabeth L. , Laskin William B.
Published: February 2021

Context.—Common fibrous histiocytoma (cFH) or dermatofibroma and dermatofibrosarcoma protuberans (DFSP) are 2 spindle cell mesenchymal tumors that are distinguished in part by their microscopic growth patterns and clinically by the greater propensity for DFSP to recur. Matrix metalloproteinases (MMPs) potentially play a role in modulating the growth patterns of cFH and DFSP by remodeling the extracellular matrix.

Objective.—To evaluate the immunohistochemical (IHC) expression of MMP-1, MMP-2, MMP-9, and MMP-14 in DFSP and cFH, because (1) MMP-1, MMP-2, MMP-9, and MMP-14 are synthesized by dermal fibroblasts, the major constituent of DFSP and cFH; and (2) platelet-derived growth factor B, which is overexpressed in most examples of DFSP because of t(17;22), activates ets-1, a transcription factor that regulates molecules associated with tumor invasion and metastasis, including MMP-1, MMP-3, and MMP-9.

Design.—Immunohistochemical studies were performed on archived, formalin-fixed, paraffin-embedded tissue of DFSP (n = 48) and cFH (n = 47).

Results.—Significant IHC expression (>10% of tumor cells) in cFH included MMP-14 (27 [59%] of 46 tumors positive), MMP-2 (21 [47%] of 45 tumors positive), MMP-9 (9 [20%] of 45 tumors positive), and MMP-1 (6 [13%] of 46 tumors positive). No DFSPs showed significant IHC expression of any of the MMPs evaluated. However, anti– MMP-2 highlighted a rich microvascular element within deep tumor tissue present in 81% of DFSPs with a prominent subcutaneous component.

Conclusion.—Our IHC results indicate that MMP-1 and MMP-9 are not up-regulated in DFSP. Convincing expression of MMP-14 in cFH suggests that this MMP may affect the growth pattern of the lesion, perhaps by activating MMP-2 expression in tumor cells. In DFSP, MMP-2 may play a role in tumor angiogenesis.
Intratesticular Angioleiomyoma
Authors: Lavis Robert , Igbokwe Uchechi , Freeman Simon , Smith Mark
Published: February 2021

Angioleiomyomas are common benign smooth muscle tumors that occur in the subcutis of the extremities and to a lesser extent, of the head and trunk. Rarely, these tumors have been reported in other deeper tissues, but never within the testis. We present what we believe to be the first report of intratesticular angioleiomyoma, occurring in a 58-year-old man with a painless testicular swelling. Orchidectomy was the treatment of choice in this patient, as there was no reliable imaging technique to clinically distinguish this benign lesion from the more common malignant intratesticular tumors.
Papular Spongiotic Dermatitis of Smallpox Vaccination: Report of 2 Cases With Review of the Literature
Authors: Gaertner Erich M. , Groo Stephen , Kim Jessica
Published: February 2021

We report 2 cases of nonspecific postvaccinial dermatitis following smallpox vaccination. The patients presented with diffuse, pruritic, erythematous macules and papules 11 days (case 1) and 7 days (case 2) following routine smallpox vaccination. Biopsies of the lesions demonstrated spongiotic dermatitis without evidence of viral cytopathic changes. One case showed a pityriasis rosea–like histologic pattern. The exanthema resolved without sequelae with symptomatic treatment (case 1). Review of historical literature demonstrated the association of a variety of nonspecific cutaneous complications with vaccinia inoculation, including erythema multiforme, urticaria, and pityriasis rosea. The association of these various dermatitides with smallpox immunization is not well known and is likely underreported.
Detection of Tumor Markers Including Carcinoembryonic Antigen, APC, and Cyclin D2 in Fine-Needle Aspiration Fluid of Breast
Authors: Lee Ahwon , Kim Yonggoo , Han Kyungja , Kang Chang Suk , Jeon Hae Myung , Shim Sang In
Published: February 2021

Context.—The traditional triple test for breast cancer diagnosis is physical examination, mammography, and aspiration cytology. However, the accuracy of mammography on young women with nonatrophied breasts is poor compared with that for women older than 50 years, and additional methods for diagnosis of breast cancer are needed.

Objective.—To investigate whether carcinoembryonic antigen (CEA), CA 15-3, and CA 125 concentrations in breast aspiration fluid are useful as breast cancer biochemical markers and whether APC and cyclin D2 gene promoter hypermethylation could be regarded as a breast cancer molecular marker.

Design.—CEA, CA 15-3, and CA 125 concentrations were measured, and methylation status of the APC gene promoter 1A and the promoter region of the cyclin D2 gene were analyzed using a methylation-specific polymerase chain reaction assay of ex vivo breast aspiration fluid obtained from 49 samples of excised breast tissue.

Setting.—The specimens were collected during a 1-year period in the tertiary care teaching hospital in Seoul, Korea.

Patients.—Forty-nine patients with breast masses were surgically treated. Thirty-four patients had breast cancer, and 15 had benign breast disease.

Results.—Aspiration fluid CEA concentrations were significantly higher in breast cancer cases than in cases of benign breast disease (mean, 69.90 ng/mg protein vs 0.68 ng/mg protein, respectively; P < .001). At 90% specificity of the assay (CEA, 2.13 ng/mg protein), the corresponding sensitivity for breast cancer detection was 62%, according to the receiver operating characteristic curve drawn. The APC gene promoter 1A and the promoter region of the cyclin D2 gene were methylated in 42% (14/33) and 70% (23/33) of the breast cancer aspiration fluid samples, respectively. A cumulative incidence of methylation of these 2 genes was 85% (28/33). The APC and cyclin D2 gene promoters were both unmethylated in the aspiration fluids from 19 women with nonmalignant breast disease.

Conclusions.—Breast aspiration fluid CEA concentration and the methylation of the APC gene promoter 1A and the promoter region of the cyclin D2 gene can be used as tumor markers to overcome some of the limitations of aspiration cytology. In combination with the mammogram and physical examination, assays for these markers could be used to help determine a definitive diagnosis when cytologic results are suspicious for malignancy.
Epithelioid Hemangioendothelioma of the Suprasellar Area: A Case Report and Review of the Literature
Authors: Baehring Joachim M. , Dickey Phillip S. , Bannykh Sergei I.
Published: February 2021

Intra-axial involvement of the brain by an epithelioid hemangioendothelioma is rare, and biological properties of the tumor are uncertain. Most of the primary brain manifestations are confined to the cerebral hemispheres. We report magnetic resonance imaging and microscopic findings of a case of suprasellar involvement by an epithelioid hemangioendothelioma. The tumor was treated with a subtotal resection only, and no progression of the disease was noted during a 6-month follow-up. Review of the literature suggested that most epithelioid hemangioendotheliomas in the brain are unifocal tumors with a rather favorable clinical outcome.
Cytosine Arabinoside Substitution Decreases Transcription Factor–DNA Binding Element Complex Formation
Authors: Zhang Ximbo , Kiechle Frederick L.
Published: February 2021

Context.—The pyrimidine nucleoside analog, cytosine arabinoside (Ara-C), is an effective therapeutic agent for acute leukemia. The phosphorylated triphosphate, cytosine arabinoside triphosphate, competes with deoxycytosine triphosphate as a substrate for incorporation into DNA. Once incorporated into DNA, it inhibits DNA polymerase and topoisomerase I and modifies the tertiary structure of DNA.

Objective.—To determine if the substitution of Ara-C for cytosine in double-stranded oligonucleotides that contain 4 specific transcription factor binding sites (TATA, GATA, C/EBP, and AP-2α) alters transcription factor binding to their respective DNA binding elements.

Design.—Transcription factors were obtained from nuclear extracts from human promyelocytic leukemia HL-60 cells. [32P]-end-labeled double-stranded oligonucleotides that contained 1 or 2 specific transcription factor binding sites with or without Ara-C substitution for cytosine were used to assess transcription factor binding by electrophoretic mobility shift assay.

Results.—The substitution of Ara-C for cytosine within and outside the transcription factor binding element (AP-2α, C/EBP), outside the binding element only (GATA, TATA), or within the binding element only (AP-2α) all result in a reduction in transcription factor binding to their respective DNA binding element.

Conclusion.—The reduction of the binding capacity of transcription factors with their respective DNA binding elements may depend on structural changes within oligonucleotides induced by Ara-C incorporation. This altered binding capacity of transcription factors to their DNA binding elements may represent one mechanism for Ara-C cytotoxicity secondary to inhibition of transcription of new messenger RNAs and, subsequently, translation of new proteins.
Microdissection Techniques for Molecular Testing in Surgical Pathology
Authors: Hunt Jennifer L. , Finkelstein Sydney D.
Published: February 2021

Objective.—To describe the techniques for microdissection of paraffin-embedded and frozen tissue sections for the use in molecular applications.

Data Sources.—Original research papers and review papers and the authors' personal experiences.

Data Synthesis.—Manual and laser-capture microdissection are described in detail, with specific protocols for sample preparation and instructions for performing the microdissection. A section addressing frequently asked questions is also included.

Conclusions.—Microdissection is a technique that is very useful both in the research setting and for clinical molecular testing in paraffin-embedded tissue samples. The available techniques range from simple and inexpensive (manual microdissection) to complex and expensive (laser-capture microdissection). All of the techniques, however, require the user to be familiar with microscopy and histology.
Frequent Expression of Human Carcinoma-Associated Antigen, a Mucin-Type Glycoprotein, in Cells of Prostatic Carcinoma
Authors: Li Rongshan , Yao Jorge L. , Bourne Patricia A. , di Sant'Agnese P. Anthony , Huang Jiaoti
Published: February 2021

Context.—Human carcinoma-associated antigen (HCA) is a mucin glycoprotein recognized by antibodies raised against epiglycanin, the latter having been originally purified from mouse mammary carcinoma cells. Human carcinoma-associated antigen expression is increased in sera of patients with various carcinomas, including prostatic carcinoma. However, to our knowledge, expression of HCA in benign and neoplastic prostatic tissue has not been studied.

Objective.—To compare the expression of HCA in cells of primary and metastatic prostatic carcinomas with its expression in non–carcinoma-associated cells.

Design.—We studied 40 cases of primary and 36 cases of metastatic prostatic carcinomas by immunohistochemical staining with anti-HCA monoclonal antibodies G1 and HAE3. The blocks from primary carcinomas also contained normal prostatic tissue (40 cases), benign prostatic hyperplasia (16 cases), and high-grade prostatic intraepithelial neoplasia (32 cases).

Results.—The 2 antibodies stained carcinomas more frequently than normal prostatic tissue, hyperplasia, and prostatic intraepithelial neoplasia (P < .001). The differences in the staining of low-grade versus high-grade tumors was not statistically significant with either antibody. The staining was present in the cytoplasm and on the luminal membrane surface of the tumor cells and in the luminal secretions. In metastatic prostatic carcinomas, G1 and HAE3 staining was positive in 44% and 67% of the cases, respectively.

Conclusions.—Our results showed that mucin protein HCA is overexpressed in cells of prostatic carcinoma, which may have value in diagnosis and therapy. Its role in carcinogenesis also merits further study.
Physician Survey of a Laboratory Medicine Interpretive Service and Evaluation of the Influence of Interpretations on Laboratory Test Ordering
Authors: Laposata Martha E. , Laposata Michael , Van Cott Elizabeth M. , Buchner Dion S. , Kashalo Mohammed S. , Dighe Anand S.
Published: February 2021

Context.—Complex coagulation test panels ordered by clinicians are typically reported to clinicians without a patient-specific interpretive paragraph.

Objectives.—To survey clinicians regarding pathologist-generated interpretations of complex laboratory testing panels and to assess the ability of the interpretations to educate test orderers.

Design.—Surveys were conducted of physicians ordering complex coagulation laboratory testing that included narrative interpretation. Evaluation of order requisitions was performed to assess the interpretation's influence on ordering practices.

Setting.—Physicians ordering coagulation testing at a large academic medical center hospital in Boston, Mass, and physicians from outside hospitals using the academic medical center as a reference laboratory for coagulation testing.

Outcome Measures.—Physician surveys and evaluation of laboratory requisition slips.

Results.—In nearly 80% of responses, the ordering clinicians perceived that the interpretive comments saved them time and improved the diagnostic process. Moreover, the interpretations were perceived by ordering clinicians to help prevent a misdiagnosis or otherwise impact the differential diagnosis in approximately 70% of responses. In addition, interpretations appeared to be able to train the ordering clinicians as to the standard ordering practices.

Conclusions.—The results demonstrate physician satisfaction with an innovative information delivery approach that provides laboratory diagnostic interpretation and test-ordering education to clinicians in the context of their daily workflow.
Clear Cell Renal Cell Carcinoma With Syncytial Giant Cells: A Case Report and Review of the Literature
Authors: Shen Rulong , Wen Ping
Published: February 2021

Renal cell carcinoma with syncytial giant cells (SGCs) is rare; to our knowledge, there are only 3 cases reported in the English literature. We report on a case that, unlike previous reports, was associated with higher grade renal cell carcinoma and an aggressive behavior. A 63-year-old man with gross hematuria was found to have a large left renal mass and no evidence of metastasis. The nephrectomy specimen contained a 14.8-cm mass that was confined within the renal capsule. Microscopically, a 1.8-cm area of SGCs was noted in a background of clear cell renal cell carcinoma of Fuhrman nuclear grades 2 to 4. The SGCs had voluminous cytoplasm, multiple large nuclei with prominent nucleoli, and focal emperipolesis. Identical to the background mononuclear tumor cells, the SGCs were positive for AE1/AE3, vimentin, and epithelial membrane antigen and negative for CD68, β-human chorionic gonadotropin, and mucin. Three months after surgery, the patient developed metastases in the liver, right kidney, and lungs.
Multiple Cavernous Hemangiomas of the Lung: A Case Report and Review of the Literature
Authors: Fine Samson W. , Whitney Kathleen D.
Published: February 2021

Cavernous hemangiomas are benign vascular tumors most commonly seen in the head and neck region in childhood. They have been described rarely in the lungs. We describe a patient with incidental pulmonary nodules discovered at autopsy, which measured up to 0.9 cm and which were present in the lung parenchyma, as well as on the pleura. The nodules were composed of dilated vascular spaces lined by flattened bland cells. Immunohistochemical studies of the lining cells revealed CD34 and factor VIII immunoreactivity, consistent with a lesion of endothelial origin. Taken together, the gross, microscopic, and immunohistochemical findings support the diagnosis of multiple pulmonary cavernous hemangiomas.
Reflectance Spectroscopy of Clotting Blood: A Description of the Time-Dependent Behavior
Authors: Greco Frank A.
Published: February 2021

Context.—Research into whether cyclooxygenase-2 (COX-2) inhibitors affect thrombosis has been hampered by the lack of a specific assay. Erythrocytes modulate the effect of aspirin on platelets, which suggests that tests of whole blood clotting may be more sensitive.

Objectives.—To determine whether reflectance spectroscopy of clotting blood generates useful information about coagulation and whether it shows an effect of COX-2 inhibitors.

Design.—A survey of 14 adults examined the range of phenomena demonstrated by reflectance spectroscopy. These phenomena were compared before and after treatment with a COX-2 inhibitor in 4 subjects.

Setting.—Out-patient clinic.

Main Outcome Measure.—Reflected light intensity was measured from blood as it clotted in a cuvette thermostated at 37°C.

Results.—The survey of healthy adults showed that the time course of reflected light intensity is similar at all wavelengths and may be divided into 4 stages: a monotonic decrease, a sigmoidal increase, a linear region, and a terminal phase. Clot formation as determined by tube inversion occurs at the transition between the first and second phases; the sigmoidal increase cannot be due to fibrin polymerization. The terminal phase coincides with clot retraction. Similar results are obtained in native whole blood and in recalcified citrated blood. Cyclooxygenase-2 inhibitors have an intrinsic effect on the sigmoidal increase ex vivo (P < .001).

Conclusions.—Reflectance spectroscopy generates unique information about clotting blood. It is feasible to use anticoagulated blood to elucidate the events underlying the time course and to investigate the effects of COX-2 inhibitors.
Clinicopathologic Study of Hepatic Penicillium marneffei in Northern Thailand
Authors: Yousukh Amnat , Jutavijittum Prapan , Pisetpongsa Pises , Chitapanarux Taned , Thongsawat Satawat , Senba Masachika , Toriyama Kan
Published: February 2021

Context.—Penicillium marneffei, an opportunistic fungus, is endemic in Southeast Asia, especially in human immunodeficiency virus–infected individuals living in northern Thailand.

Objective.—We present the results of a clinicopathologic study of hepatic penicilliosis among human immunodeficiency virus/acquired immunodeficiency syndrome patients.

Design.—A search of liver biopsies in one institution from 1998 to 1999 identified 30 cases of penicilliosis.

Results.—Histologically, hepatic lesions could be classified into 1 of 3 patterns: diffuse, granulomatous, and mixed. The diffuse pattern showed a diffuse infiltration of foamy macrophages that contained numerous P marneffei. The granulomatous pattern showed a formation of multiple granulomata with various degrees of inflammatory cell infiltration. The mixed pattern showed features intermediate between the diffuse and granulomatous patterns. Liver function tests of the 3 pathologic pattern groups were evaluated, but there were no statistically significant differences in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase levels among the various histologic groups.

Conclusion.—To our knowledge, this is the largest series to date that documents the liver pathology that results from this pathogen. We hypothesize that the histologic patterns seen on biopsy reflect the level of the host's immunity. Hence, in addition to a diagnosis of penicilliosis, a liver biopsy may also provide an assessment of the host's immune status, whereas liver function tests do not.
Follicular Lymphoma With a Burkitt Translocation—Predictor of an Aggressive Clinical Course: A Case Report and Review of the Literature
Authors: Voorhees Peter M. , Carder Kathryn A. , Smith Scott V. , Ayscue Lanier H. , Rao Kathleen W. , Dunphy Cherie H.
Published: February 2021

Follicular lymphoma is an indolent lymphoma characterized by the (14;18) translocation, which leads to aberrant expression of Bcl-2. Translocations involving 8q24 are most commonly associated with Burkitt lymphoma and result in c-Myc overexpression. We report a case of follicular lymphoma of predominant small cleaved-cell type (grade 1) associated with both a t(14;18)(q32;q21) and a t(8;22)(q24;q11). The 8q24 translocation predicted an aggressive clinical course, as the lymphoma transformed into acute lymphoblastic leukemia within a year of initial diagnosis. Routine cytogenetic analysis is recommended at initial diagnosis of follicular lymphoma to better identify abnormalities that may predict prognosis and influence therapy.
Can Human Papillomavirus DNA Testing Substitute for Cytology in the Detection of High-Grade Cervical Lesions?
Authors: Lee Kyung-Ju , Lee Jae-Kwan , Saw Ho-Suk
Published: February 2021

Context.—High-risk human papillomaviruses (HPVs) are causal factors of cervical carcinomas.

Objective.—To evaluate the sensitivity and efficiency of HPV DNA testing in comparison with conventional cytology for detection of cervical intraepithelial neoplasia (CIN) and cancer.

Design.—Both testing procedures were administered to 593 women, aged 14 to 88 years (average, 41.7 years), who were referred for abnormal cytology from January 2000 through December 2001 at Korea University Guro Hospital (Seoul, Korea). After histologic confirmation by either colposcopically directed biopsy or endocervical curettage, the efficiency of the detection methods for high-grade cervical lesion was evaluated for the following 3 data sets: HPV DNA testing, conventional cytology, and the 2 tests combined.

Results.—The sensitivity, specificity, and positive predictive, and negative predictive values for the detection of CIN 2 or higher were 92.4%, 52.4%, 49.3%, and 93.2% for HPV DNA testing; 76.3%, 65.8%, 52.8%, and 84.7% for cytology; and 97.8%, 36.7%, 49.2%, and 97.3% for the combined tests. Among the 151 patients diagnosed with CIN 2 or CIN 3, 137 patients (90.7%) were HPV positive, 116 patients (76.8%) were proven to have abnormal cytology, and 147 patients (97.6%) were positive for either HPV DNA testing or cytology. The sensitivity values for HPV DNA testing and cytology were 97.9% (46/47) and 74.5% (35/47), respectively, for invasive cervical cancer detection, and the combined tests showed 100% (47/47) sensitivity. Depending on the patient's age and the grade of the cervical lesion, HPV DNA testing proved to be significantly more sensitive than cytology for the primary detection of cervical abnormalities (P < .001).

Conclusion.—Human papillomavirus DNA testing for the detection of high-grade cervical lesions was more sensitive than cytology alone. In addition, the screening sensitivity can be further improved by combining cytology with HPV DNA testing. This approach is especially beneficial in detecting cancer precursors in women older than 60 years.
Cytologic Features of Squamous Cell Carcinoma in ThinPrep Slides: Evaluation of Cases That Performed Poorly Versus Those That Performed Well in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology
Authors: Renshaw Andrew A. , Dubray-Benstein Barbara , Cobb Camilla J. , Lozano Richard L. , Neal Margaret H. , Prey Marianne , Schulte Michael A.
Published: February 2021

Context.—Although the cytologic features of squamous cell carcinoma in ThinPrep specimens are well known, whether these features are different in cases that are easily identified than in cases that are more difficult to identify is not known.

Objective.—To determine the cytologic features of squamous cell carcinoma in ThinPrep specimens that are easy to identify versus those that are difficult.

Design.—The cytologic features of 6 cases of squamous cell carcinoma that performed poorly in the College of American Pathologists Interlaboratory Comparison Program were compared with 14 cases that performed extremely well.

Results.—After evaluation of multiple criteria, 7 different cytologic features were analyzed based on review by a consensus panel blinded to the performance of the cases. The feature that was most strongly associated with cases that performed poorly was the presence of Trichomonas vaginalis (5/6 [83%] vs 0/14; P < .001). The presence of marked nuclear pleomorphism was more common in cases that performed well (4/14 [28%] vs 0/6; P = .27), but was not significant. The number of tumor cells, the number of normal cells, and the presence of keratinization, pleomorphism, nucleoli, and diathesis were not significant. The most common misdiagnosis after Trichomonas vaginalis was reparative change.

Conclusions.—The presence of Trichomonas is characteristic of cases of squamous cell carcinoma in ThinPrep slides that are often misdiagnosed in this program. While Trichomonas is identified by participants in some of these cases, a significant percentage of participants interpreted the findings as reparative, without identifying the organism. These results emphasize the importance of distracting factors, whether identified or not, in evaluating gynecologic cytology.
Immunohistochemical Analysis of Lung Carcinomas With Pure or Partial Bronchioloalveolar Differentiation
Authors: Peter Sarantopoulos G. , Gui Dorina , Shintaku Peter , Hong Longshen , Wang Ya-Ying , Yap Cecilia S. , Fishbein Michael C.
Published: February 2021

Context.—In 1999, the World Health Organization redefined bronchioloalveolar carcinomas (BACs) as those neoplasms with only a pure lepidic growth pattern and no invasion.

Objectives.—The present study examined 45 lung cancers with a BAC component (1) to determine whether these tumors would be classified as BACs by current World Health Organization standards, (2) to quantitate the BAC component within these tumors, and (3) to see if phenotypic differences exist between the so-called invasive and noninvasive regions of these tumors.

Design.—Retrospective review of hematoxylin-eosin–stained slides and classification of histologic grade, tumor subtype, and percentage of pure BAC pattern, with further characterization by immunohistochemical staining for thyroid transcription factor 1, cytokeratin 7, cytokeratin 20, and Ki-67 antibodies.

Results.—Only 7 (15.6%) of the 45 tumors examined could be classified as BAC by current strict World Health Organization criteria. Those tumors, classified as nonmucinous and mixed, showed similar immunohistochemical staining for cytokeratin 7, cytokeratin 20, and thyroid transcription factor 1; mucinous tumors showed disparate staining. Significant differences in immunohistochemical staining and tumor cell proliferation were seen for the regions of tumors designated as lepidic, infiltrative, and leading edge and for the regions of tumors with different histologic grades (ie, well, moderately, and poorly differentiated).

Conclusions.—Nonmucinous and mixed BACs are phenotypically similar and show identical immunohistochemical staining patterns; mucinous tumors, on the other hand, show disparate immunohistochemical staining. Pulmonary neoplasms designated as adenocarcinomas with a BAC component represent a heterogenous group with a range of cell types, differentiation, growth, and immunophenotypes. Within an individual neoplasm, there are regional differences in these parameters as well.
Evaluation of a Dimeric Inhibin-A Assay for Assessing Fetal Down Syndrome: Establishment, Comparison, and Monitoring of Median Concentrations for Normal Pregnancies
Authors: Erickson J. Alan , Ashwood Edward R. , Gin Cynthia A.
Published: February 2021

Context.—Several studies report the role of dimeric inhibin-A in assessing risk for fetal Down syndrome. The majority, however, use the Serotec inhibin-A assay and not the newer Diagnostic Systems Laboratories inhibin-A enzyme-linked immunosorbent assay (ELISA).

Objectives.—To establish normal gestational age day-specific medians, to compare our results against previous studies pertaining to the inhibin-A ELISA, and to evaluate long-term assay performance.

Design.—Using the inhibin-A ELISA, 100 specimens were assayed for each completed week of gestation for weeks 15 to 20, 50 specimens for 14 weeks, and 54 specimens for 21 weeks or older. Regressed inhibin-A medians were calculated employing a second-degree polynomial fit of the arithmetic medians. Thereafter, inhibin-A ELISA lot comparisons were performed to evaluate consistency.

Results.—Regressed values of 182, 174, 175, 184, 201, and 226 pg/mL resulted for weeks 15 to 20, respectively [pg/mL inhibin-A = 4.1528(gestational age)2 − 136.49(gestational age) + 1294.9]. A comparison with 2 other studies shows our values to be lower overall by 15 ± 11.4% and 16 ± 2.6%. However, variability between kit lots was as high as 30%.

Conclusions.—The equation derived provides for the calculation of gestational age day-specific inhibin-A medians for integration into maternal serum screening programs with a subsequent decrease in false-positives expected and observed. Our medians differ considerably from those of other studies, with limited data, using the Diagnostic Systems assay. However, lot changes since the initial analysis have exhibited similar inconsistencies. Therefore, we recommend that others incorporating the assay into their screening programs carefully establish, monitor, and adjust their medians accordingly as a result of potential variations.
Role of PTEN in Gastrointestinal Stromal Tumor Progression
Authors: Ricci Riccardo , Maggiano Nicola , Castri Federica , Rinelli Alessandro , Murazio Marino , Pacelli Fabio , Potenza Angelo Eugenio , Vecchio Fabio Maria , Larocca Luigi Maria
Published: February 2021

Context.—Gastrointestinal stromal tumors (GISTs) are Kit/CD117-expressing mesenchymal neoplasms of uncertain malignant potential. The lack of a reliable method of prognostication hampers the selection of patients eligible for STI571 therapy. 10q22-q23 is a region involved in chromosomal losses found in a fraction of malignant primary and metastatic GISTs harboring PTEN (phosphatase and tensin homologue deleted on chromosome 10), a tumor suppressor gene often altered in human neoplasms.

Objective.—To investigate the role of PTEN in GISTs, an issue that to our knowledge has not been addressed previously.

Design.—PTEN status was determined in a series of 21 GISTs, with follow-up ranging between 6 and 198 months, using immunohistochemistry correlated with clinical data.

Results.—A greater than 25% fraction of cells with low or absent PTEN immunostaining was detected in 9 GISTs, including all those showing malignancy. By the log-rank test, a fraction of PTEN-deficient cells greater than 25% was associated with malignancy (P < .001). Percentage of cells underexpressing PTEN, size, cellularity, MIB-1 immunoreactivity, and coagulative necrosis proved to be associated with malignancy by Cox proportional hazards univariate analysis; low or absent expression of PTEN was the only factor selected by multivariate analysis (P = .03).

Conclusions.—PTEN downregulation is implied in GIST progression. The immunohistochemical assessment of PTEN status appears to be a promising method of GIST prognostication.
Hemoglobin C and Hemoglobin O-Arab Variants Can Be Diagnosed Using the Bio-Rad Variant IIHigh-Performance Liquid Chromatography SystemWithout Further Confirmatory Tests
Authors: Joutovsky Alla , Nardi Michael
Published: February 2021

Context.—Current standards for laboratory accreditation from the College of American Pathologists state that when high-performance liquid chromatography (HPLC) is used as a screening test, all non-A, non-S abnormal hemoglobin (Hb) variants must be confirmed by an alternative method, including alkaline and acid electrophoresis.

Objective.—To determine whether confirmation of Hb C and Hb O-Arab variants by an alternative method is required when using the Bio-Rad Variant II HPLC system.

Design.—We reviewed 48 478 consecutive hemoglobin identification test results performed on the Bio-Rad Variant II HPLC system during the period November 15, 2000 to January 15, 2003.

Setting.—Special Hematology Laboratory, Department of Pathology, Bellevue Hospital Center, New York, NY.

Main Outcome Measures.—The chromatogram patterns and retention times (RTs) for specimens containing Hb C and Hb O-Arab were analyzed. We compared the results by the HPLC method with those by the confirmatory tests (alkaline and acid electrophoresis) for both variants.

Results.—We identified 3668 cases of abnormal hemoglobin variants, including 660 cases of Hb C trait (17%), 5 cases of Hb O-Arab trait (0.1%), and 1 case of Hb SO-Arab (0.03%). A unique pattern of separation on the chromatogram for Hb O-Arab was revealed, presenting as 2 distinct peaks in 2 different manufacturer-defined RT windows, namely, D and C. The chromatogram for Hb C did not show the D window in any of the reviewed cases. The RT in the C window (C-RT) revealed a statistically significant difference for Hb C and Hb O-Arab (5.18 ± 0.01 minutes and 4.91 ± 0.01 minutes, respectively; P < .001).

Conclusion.—According to our review, the identification of Hb C and Hb O-Arab is accurate using HPLC methodology, as performed by the Bio-Rad Variant II HPLC system. This method can be both confirmatory and diagnostic at the same time.
Malignant Gastrointestinal Leiomyosarcoma and Gastrointestinal Stromal Tumor With Prominent Osteoclast-like Giant Cells
Authors: Insabato Luigi , Di Vizio Dolores , Ciancia Giuseppe , Pettinato Guido , Tornillo Luigi , Terracciano Luigi
Published: February 2021

Context.—One case of leiomyosarcoma and one case of gastrointestinal stromal tumor with prominent osteoclast-like giant cells have so far been reported in the digestive tract.

Objective.—To ascertain the clinicopathologic features and biologic behavior of these tumors, we report 3 additional cases of leiomyosarcoma of the gastrointestinal tract and one malignant gastrointestinal stromal tumor.

Design.—Histologic and immunohistochemical examinations were performed. Clinical and follow-up data were recorded, and the literature was reviewed.

Results.—The age of the patients ranged from 50 to 68 years (mean, 62 years). One of the lesions arose in the stomach, one in the ileum, and 2 in the colon. Three tumors showed a strong positivity for muscle actin and desmin and were diagnosed as leiomyosarcomas, 2 of them showing spindle cells and 1 of them showing epithelioid cells. The fourth tumor reacted strongly positive for c-Kit (CD117) and vimentin, and it was diagnosed as an epithelioid malignant gastrointestinal stromal tumor. All tumors were characterized by numerous osteoclast-like giant cells that were unevenly distributed and that, using immunohistochemistry, reacted strongly with CD68.

Conclusions.—Malignant stromal tumors with osteoclast-like giant cells of the gastrointestinal tract are rare entities, are more commonly of a myogenic origin such as leiomyosarcoma, and seem to have an aggressive behavior.