bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant Melanoma
Authors: Slominski Andrzej , Wortsman Jacobo , Carlson Andrew J. , Matsuoka Lois Y. , Balch Charles M. , Mihm Martin C. 
Published: January 2021

AbstractContext.—The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic techniques and potential therapeutic approaches.Objectives.—To present the most current concepts on the etiology and pathogenesis of melanoma and to introduce the recent diagnostic techniques and the potential therapeutic approaches.Methods.—Data sources were reports on melanoma published in the English language literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola University Medical Center, and University of Tennessee Health Science Center.Results.—Studies on melanoma containing chromosomal or genetic evaluation were selected for further analysis. Current clinical and pathologic categories with the reported genetic abnormalities were related to the latest information on pigment biology. The data extracted were used to develop a conceptual framework on the pathogenesis of melanoma; the generated model was then evaluated and used to suggest potential therapeutic approaches.Conclusions.—(1) Melanoma is not genetically homogenous, and the existing differences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension, ulceration of primary tumor, and metastatic process, have profound prognostic and therapeutic implications. (2) Chromosomal aberrations and gene mutations are found in sporadic and familial melanomas; among the most important are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expression is associated with more aggressive behavior. (3) Melanoma cells possess a remarkable repertoire of biosynthetic capacities represented by the production of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products α-melanocyte-stimulating hormone and adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, but also as potential targets for melanoma therapy.
Immunohistochemical Analysis of Nuclear Versus Cytoplasmic Staining of WT1 in Malignant Mesotheliomas and Primary Pulmonary Adenocarcinomas
Authors: Foster Matthew R. , Johnson Joyce E. , Olson Sandy J. , Allred D. Craig 
Published: January 2021

Abstract
Context.—Previous studies have indicated certain immunohistochemical markers, including WT1, may be helpful in distinguishing adenocarcinomas from mesotheliomas, but to date there are no reliable, widely accepted, commercially available antibodies positive in mesotheliomas and negative in adenocarcinomas. We compared the nuclear and cytoplasmic staining patterns of WT1 in these 2 malignancies using a commercially available antibody and examined the expression of 2 other previously reported positive markers, calretinin and thrombomodulin.
Methods.—Sixty-seven mesotheliomas and 51 adenocarcinomas, all paraffin embedded, were retrieved from recent case files. The diagnosis of mesothelioma was based on typical clinical and morphologic features, as well as immunohistochemistry; electron microscopy had been performed on 16 cases. The diagnosis of adenocarcinoma was based on typical light microscopic findings and a positive stain for mucin. Commercially available antibodies to WT1, thrombomodulin, and calretinin were applied. Because of the conflict surrounding calretinin, 2 anticalretinin antibodies (from Chemicon Inc and Zymed Laboratories) were utilized.
Results.—Fifty of 67 mesotheliomas showed strong nuclear staining with WT1. No adenocarcinomas (0/51) showed nuclear staining. Twenty-three of 67 mesotheliomas were positive for thrombomodulin, and 35 of 67 mesotheliomas were positive for calretinin with the Chemicon antibody. Nine of 15 mesotheliomas were positive for calretinin with the Zymed antibody.
Conclusions.—Thrombomodulin and calretinin did not prove useful in discriminating between mesotheliomas and adenocarcinomas. The degree of positivity with calretinin may be dependent on the specific antibody utilized. Nuclear staining for WT1 is highly specific for mesothelioma and, in the appropriate clinical setting, can be a helpful adjunct in the distinction between adenocarcinomas and mesotheliomas.
Urothelial and Prostate Carcinoma Metastasizing to the Same Lymph Node
Authors: Overstreet Kerith , Haghighi Parviz 
Published: January 2021

Abstract
We report herein a case of a collision tumor composed of high-grade urothelial carcinoma and a Gleason grade 3+4 prostate adenocarcinoma metastasizing to the same lymph node. After the patient underwent cystoprostatectomy for known urothelial carcinoma, he was incidentally discovered to have a second primary prostate tumor. Lymph node examination revealed that one node appeared to have metastatic foci from both primary tumors. The presence of 2 tumor types colliding in the same lymph node was confirmed using immunohistochemical stains, including monoclonal carcinoembryonic antigen, prostate-specific antigen, prostatic acid phosphatase, cytokeratins 7 and 20, and CD57. We also stained both primary tumors with the same panel as an internal control. Although 2 similar collision tumors have been reported in the literature in the past, neither used a battery of immunohistochemical stains to definitively distinguish one tumor from the other. Herein, we review the literature on urothelial and prostate collision tumors and some of the special stains used to distinguish them.
Malignancies Arising in Oncocytic Schneiderian Papillomas
Authors: Maitra Anirban , Baskin Leland B. , Lee Edward L. 
Published: January 2021

Abstract
Oncocytic schneiderian papillomas (OSPs) are uncommon benign neoplasms that arise from the sinonasal schneiderian epithelium. Malignancies arising in OSPs are rare, and, to our knowledge, only 14 such instances have been reported in the medical literature. We report 2 additional cases—a small cell carcinoma and a sinonasal undifferentiated carcinoma arising in OSPs and presenting synchronously with the benign neoplasm. The potential for malignant transformation in OSPs is small, but warrants that these papillomas be completely excised to exclude a coexisting carcinoma.
Invasive Secretory (Juvenile) Carcinoma Arising in Ectopic Breast Tissue of the Axilla
Authors: Shin Sandra J. , Sheikh Farrukh S. , Allenby Patricia A. , Rosen Paul Peter 
Published: January 2021

Abstract
Mammary carcinoma arising in ectopic breast tissue is an uncommon occurrence. Most reported cases have involved ductal carcinoma, but other types, such as medullary, papillary, and lobular carcinomas, have been described. For pathologists, the diagnosis of mammary carcinoma arising in ectopic breast tissue can be difficult, especially in the axilla, where carcinoma of adnexal origin must be excluded. We describe a 46-year-old woman who developed invasive (juvenile) secretory carcinoma in ectopic right axillary breast tissue and micrometastatic carcinoma in an ipsilateral axillary lymph node. The carcinoma arose in a right axillary mass that had been present for 8 years, from which she had secreted fluid during prior breast-feeding. To our knowledge, this is the first report of secretory carcinoma arising in axillary breast tissue to be documented in the current literature.
Achondrogenesis Type IB
Authors: Corsi Alessandro , Riminucci Mara , Fisher Larry W. , Bianco Paolo 
Published: January 2021

Abstract
Achondrogenesis type IB is a lethal osteochondrodysplasia caused by mutations in the diastrophic dysplasia sulfate transporter gene. How these mutations lead to the skeletal phenotype is not known. Histology of plastic-embedded skeletal fetal achondrogenesis type IB samples suggested that interterritorial epiphyseal cartilage matrix was selectively missing. Cartilage was organized in “chondrons” separated by cleft spaces; chondrocyte seriation, longitudinal septa, and, in turn, mineralized cartilaginous septa were absent. Agenesis of interterritorial matrix as the key histologic change was confirmed by immunohistology using specific markers of territorial and interterritorial matrix. Biglycan-enriched territorial matrix was preserved; decorin-enriched interterritorial areas were absent, although immunostaining was observed within chondrocytes. Thus, in achondrogenesis type IB: (1) a complex derangement in cartilage matrix assembly lies downstream of the deficient sulfate transporter activity; (2) the severely impaired decorin deposition participates in the changes in matrix organization with lack of development of normal interterritorial matrix; and (3) this change determines the lack of the necessary structural substrate for proper endochondral bone formation and explains the severe skeletal phenotype.
Aortic and Mitral Fenfluramine-Phentermine Valvulopathy in 64 Patients Treated With Anorectic Agents
Authors: Volmar Keith E. , Hutchins Grover M. 
Published: January 2021

Abstract
Context.—Few published studies of the pathology of fenfluramine-phentermine (fen-phen) valvulopathy, described by Connolly and colleagues in 1997, have appeared.
Objectives.—To define temporal changes in the morphology of the stuck-on plaques and to determine whether the plaques progress or regress after cessation of fen-phen.
Methods.—The available clinical information and pathology material from 35 aortic valves (AVs) and 43 mitral valves (MVs) from 64 patients were reviewed.
Results.—The valves fell into 3 groups: 17 AVs and 28 MVs had fen-phen lesions only, 2 AVs and 7 MVs had fen-phen changes associated with other valve diseases, and 16 AVs and 8 MVs had no fen-phen changes. Fenfluramine-phentermine–attributable dysfunction was regurgitation in all instances. Typical plaques showed proliferation of myofibroblastic cells with myxoid stroma. Small vascular channels and slight lymphocytic accumulations were often present. Deeper parts of some plaques had dense fibroelastic tissue underlying typical plaque.
Conclusions.—Considerable individual variation in the time course of anorectic agent use and the severity of fen-phen valvulopathy was observed. Possible plaque regression could not be assessed from this study. The observations suggest that in some patients fen-phen–induced plaques may continue to have surface proliferation despite drug withdrawal.
Clear Cell Odontogenic Carcinoma
Authors: Li Tie-Jun , Yu Shi-Feng , Gao Yan , Wang En-Bo 
Published: January 2021

Abstract
Context.—Odontogenic tumor composed predominantly of clear cells is a rare neoplasm of the jaws that was initially designated as clear cell odontogenic tumor. Subsequent reports in the literature, however, all have indicated that this tumor exhibits an aggressive behavior characterized by infiltrative local growth, recurrence, or metastases.
Objective.—To ascertain the clinicomorphologic features and biologic behavior of this tumor group, we present 5 additional cases using the term clear cell odontogenic carcinoma.
Design.—Histologic and immunohistochemical examinations were performed on clear cell odontogenic carcinomas from 5 patients. Clinical and follow-up data were recorded, and the literature was reviewed.
Results.—The patients were 1 man and 4 women with an average age of 42.4 years at diagnosis. Three tumors occurred in the mandible and the other 2 in the maxilla. Four of the 5 cases occurred in the anterior or premolar areas of the jaws, appearing as poorly marginated radiolucencies. All cases consisted of islands and sheets of large clear cells and small basaloid cells with scanty eosinophilic cytoplasm, which were separated by thin, mature, fibrous septae. The tumors were unencapsulated and showed aggressive infiltration of the surrounding muscle and perineural tissues. Most of the clear cells contained cytoplasmic glycogen. Immunocytochemically, the tumor cells were positive for pan-keratin, cytokeratin 19, and epithelial membrane antigen, but were negative for vimentin, S100 protein, desmin, smooth muscle actin, human melanoma antigen (HMB-45), and α1-antichymotrypsin. Follow-up data showed 4 of 5 patients to have multiple local recurrences, and 1 of these 4 had submandibular lymph node metastasis and a fatal outcome due to uncontrollable tumor growth.
Conclusion.—These results suggest that odontogenic clear cell neoplasms are at least low-grade malignancies and should be classified as carcinomas.
Contribution of Nonsteroidal Anti-inflammatory Drugs to Deaths Associated With Peptic Ulcer Disease
Authors: Tsokos Michael , Schmoldt Achim 
Published: January 2021

Abstract
Context.—Of the side effects occurring in temporal association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), peptic ulcer disease is reported most often.
Objectives.—To (1) provide information on the temporal association between fatal peptic ulcer presenting as sudden death and NSAID use prior to death, and (2) to examine the diagnostic efficiency of postmortem determination of NSAID levels using high-pressure liquid chromatography.
Design.—Prospective autopsy study of all cases of sudden death associated with peptic ulcer disease from a total of 1139 medicolegal autopsies performed during a 12-month period.
Methods.—Postmortem femoral blood samples were analyzed for NSAIDs using high-pressure liquid chromatography, and specimens of gastric and duodenal mucosa were examined for coexisting pathologic conditions.
Results.—Twelve fatalities that occurred out of hospital as a result of peptic ulcer disease and presented as sudden death were identified. Autopsy blood samples were positive for NSAIDs in 7 cases (ibuprofen in 4 cases, levels 0.8 to 1.4 μg/mL; diclofenac in 2 cases, levels 0.6 and 1.6 μg/mL; and ketoprofen in 1 case, level 0.3 μg/mL). The ages of the affected individuals (3 men, 4 women) ranged from 43 to 60 years. No other drugs, including corticosteroids, anticoagulants, salicylic acid, and salicylates, were present. Microscopic examination revealed no pathologic antemortem mucosal conditions in any of the cases.
Conclusions.—For the postmortem elucidation of etiopathogenetic factors contributing to fatal peptic ulcer disease, high-pressure liquid chromatography to determine NSAID levels in autopsy blood samples is of considerable diagnostic benefit, especially when combined with histology. The number of cases of sudden death involving younger individuals dying as a result of peptic ulcer disease in temporal association with preceding use of NSAIDs seems to be underestimated from the clinical viewpoint due to the underrepresentation of out-of-hospital fatalities in the field of clinical pathology.
Aspiration Cytology of Pediatric Solitary Papillary Hyperplastic Thyroid Nodule
Authors: Khurana Kamal K. , Baloch Zubair W. , LiVolsi Virginia A. 
Published: January 2021

AbstractContext.—Solitary papillary hyperplastic thyroid nodules (SPHTNs) are frequently encountered in children and teenagers. Although the histologic features are well described, to the best of our knowledge, cytologic findings have not been reported.Objectives.—To review the cytologic features of histologically proven SPHTNs and to identify the potential diagnostic pitfalls in cytologic diagnosis.Materials and Methods.—Fine-needle aspiration cytology of 3 histologically proven SPHTNs was reviewed.Results.—Two girls and 1 boy (ages 11, 12, and 15 years) were affected. The cytologic diagnosis in all 3 cases was suspicious for papillary thyroid carcinoma (PTC). The spectrum of cytologic findings included broad flat sheets and 3-dimensional clusters with fire flares. There was mild to moderate nuclear pleomorphism and nuclear atypia. Short nonbranching papillae with transgressing vessels shown to represent hyperplastic papillae on histologic sections were identified in all cases. The background contained giant cells, histiocytes, and watery and inspissated colloid. Although nuclear grooves were identified in occasional cells, intranuclear inclusions were absent. A cell block section (1 case) and histologic sections of SPHTNs (2 cases) were immunohistochemically negative for cytokeratin 19.Conclusions.—Fine-needle aspiration of SPHTNs may be difficult to interpret accurately and can result in false-positive diagnosis of PTC. Although it shares several cytologic features with PTC, the presence of fire flares and short nonbranching papillae, as well as lack of intranuclear inclusions and watery and inspissated colloid in SPHTN appear to be useful features that are helpful in distinguishing SPHTN from PTC. Negative immunohistochemical staining for cytokeratin 19 is useful in excluding a diagnosis of PTC.
Delayed Cutaneous Hypersensitivity Reactions to Hirudin
Authors: Smith Kathleen J. , Rosario-Collazo Juan , Skelton Henry 
Published: January 2021

Abstract
Hirudin is one of the new synthetic antithrombin agents, which is most commonly used in patients with type II heparin-induced thrombocytopenia and in patients with hypersensitivity reactions to unfractionated heparin as well as low-molecular-weight heparins. Hirudin is comparable to heparin as an antithrombotic agent and also has been studied as a primary treatment in patients who experienced acute myocardial infarctions. We describe a patient with a history of type II heparin-induced thrombocytopenia who was placed on intravenous hirudin therapy. After extravasation of the intravenous hirudin site, the patient developed a delayed hypersensitivity reaction that histologically showed an epithelioid granulomatous infiltrate. Although rare reports of hypersensitivity reactions to hirudin have been published, these reactions have not been well characterized and the histopathologic changes have not been described.
Unusual Clear Cell Variant of Epithelioid Mesothelioma
Authors: Dessy Enrico , Falleni Monica , Braidotti Paola , Del Curto Barbara , Panigalli Tiziana , Pietra Giuseppe G. 
Published: January 2021

Abstract
Clear cell mesothelioma is an extremely rare neoplasm of the pleura, which can easily be mistaken for a metastasis of clear cell carcinoma to the pleura. We report here the histochemical, immunohistochemical, and ultrastructural aspects of a new case of clear cell pleural mesothelioma in a 52-year-old man with no known asbestos exposure. He was admitted to the hospital for recurrent pleural effusion, which was negative for neoplastic cells at the cytologic examination. A partial decortication of the right pleura was performed. The morphologic, immunohistochemical, and ultrastructural features reported for this case are consistent with the diagnosis of clear cell mesothelioma. The differential diagnosis and immunohistochemical features in comparison with other clear cell neoplasms are discussed.
Immunohistochemical Analysis of p18INK4C and p14ARF Protein Expression in 117 Oligodendrogliomas
Authors: Korshunov Andrey , Golanov Andrey 
Published: January 2021

Abstract
Objective.—To investigate immunoexpression of 2 cyclin-dependent kinase inhibitors, p18INK4C (p18) and p14ARF (p14), in oligodendrogliomas and to evaluate the possible association with tumor grade and clinical outcome.
Design.—One hundred seventeen specially selected cases of cerebral oligodendrogliomas were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to p18INK4C (118.2) and p14ARF (FL-132) proteins. A computerized color image analyzer was used to count immunostained nuclei.
Results.—p18 nuclear immunoexpression was found in 57 (49%) of the oligodendrogliomas we studied. p18 immunoreactivity exhibited a clear tendency to elevate with increasing tumor grade, and the mean p18 labeling index was 9.7% for low-grade (World Health Organization [WHO] grade II) and 19.2% for high-grade (WHO III) tumors. p14-immunopositive nuclei were found in 87 (74%) tumors, and p14 immunoreactivity showed no correlation with oligodendroglioma histological malignancy. Survival times were significantly reduced for p18-positive tumors, and risk of death was independently associated with p18 expression (hazard ratio = 2.48; P = .01). There was no difference in survival times in patients with or without p14 immunoreactivity.
Conclusions.—p18 protein expression is closely associated with malignant oligodendrogliomas and worse clinical outcome. It seems unlikely that p14 immunohistochemistry will be of value in assessing individual prognosis for these tumors.
Melanoma Markers in Angiomyolipoma of the Liver and Kidney
Authors: Makhlouf Hala R. , Ishak Kamal G. , Shekar Raj , Sesterhenn Isabell A. , Young Denise Y. , Fanburg-Smith Julie C. 
Published: January 2021

Abstract
Context.—Melanoma markers, especially the new microphthalmia transcription factor (mitf), have not been previously compared in hepatic and renal angiomyolipomas.
Objectives.—To evaluate expression of the novel melanocytic markers mitf and tyrosinase in angiomyolipomas, and to compare these markers with the established markers HMB-45 and melan-A in both hepatic and renal tumors.
Design.—Clinical, histopathologic, and immunohistochemical features of 15 hepatic angiomyolipomas were compared with those of 10 renal angiomyolipomas.
Results.—No significant differences between patients with hepatic angiomyolipomas and renal angiomyolipomas were found with respect to age, gender, race, and tumor size. Hepatic angiomyolipomas exhibited a predominance of the epithelioid smooth muscle cell component, in contrast to their renal counterparts, which were predominantly spindled. The smooth muscle cells expressed HMB-45 in 100% of cases in both groups, melan-A in 14 of 15 hepatic angiomyolipomas and 8 of 9 renal angiomyolipomas, mitf in 5 of 12 hepatic angiomyolipomas versus 6 of 10 renal angiomyolipomas, and tyrosinase in 3 of 12 and 2 of 10 hepatic angiomyolipomas and renal angiomyolipomas, respectively. The extent and intensity of immunostaining with HMB-45 and melan-A were dependent on whether spindled or epithelioid cells predominated; the epithelioid cells showed stronger and more widespread reactivity than the spindled cells.
Conclusion.—We believe that the best immunohistochemical marker for confirming the diagnosis of angiomyolipoma is HMB-45, followed by melan-A. Routine use of mitf and/or tyrosinase is not indicated.