bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Nonsteroidal Anti-inflammatory Drugs to Deaths Associated With Peptic Ulcer Disease
Authors: Tsokos Michael , Schmoldt Achim
Published: January 2021

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

Context.—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

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

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

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

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.
Identification of Numerical Chromosomal Changes Detected by Interphase Fluorescence In Situ Hybridization in High-Grade Prostate Intraepithelial Neoplasia as a Predictor of Carcinoma
Authors: Al-Maghrabi Jaudah , Vorobyova Lada , Toi A. , Chapman William , Zielenska Maria , Squire Jeremy A.
Published: January 2021

Context.—High-grade prostate intraepithelial neoplasia (HPIN) is the most likely precursor of prostate cancer. The condition of many patients with a diagnosis of HPIN in prostate needle core biopsy could, if left untreated, progress to invasive cancer. Currently there is no available clinical, immunohistochemical, or morphologic criteria that are predictive of this progression.

Objective.—To determine whether chromosomal instability in these precursor lesions could increase their predictive value for cancer detection.

Design.—Dual-color interphase fluorescence in situ hybridization analysis was performed on archived prostate needle core biopsies from 54 patients with initial diagnosis of isolated HPIN and follow-up of 3 years or more. We used commercially available centromere probes for chromosomes 4, 7, 8, and 10. We had interpretable results in 44 patients as follows: (1) group A: 24 HPIN patients with persistent HPIN and/or benign lesions in the follow-up biopsies, and (2) group B: 20 HPIN patients with progression to prostate carcinoma.

Results.—Twenty-five percent of the patients in group B displayed numeric chromosomal aberrations. Only 8.3% of the patients from group A had chromosomal abnormalities (P = .1). The observed overall chromosomal changes in HPIN were higher than those in normal or hyperplastic epithelium, with a statistically significant difference (P < .05). All aberrations were detected in the form of chromosomal gain. Overall, the commonest aberration was gain of chromosome 8, followed by gains of chromosomes 7 and 10.

Conclusion.—These results indicated that although no single numeric chromosomal abnormality could be assigned as a predictor of HPIN progression to carcinoma, the overall level of numeric chromosomal abnormalities shows a trend of elevation in HPIN patients whose condition subsequently progressed to carcinoma.
Pseudallescheriasis as an Aggressive Opportunistic Infection in a Bone Marrow Transplant Recipient
Authors: Nonaka Daisuke , Yfantis Harris , Southall Pamela , Sun Chen-Chih
Published: January 2021

Pseudallescheria boydii is a low-virulence fungus that is the main causative agent of posttraumatic mycetoma in a nonimmunocompromised host. Immunocompromised patients are at high risk for locally invasive or disseminated Pseudallescheria infection. However, aggressive opportunistic infections due to P boydii are reported infrequently because it morphologically resembles other fungi, especially Aspergillus species, on tissue histology; therefore, such infections are not identified and treated properly. We report a case of disseminated P boydii infection in a patient following bone marrow transplantation. The identity of the fungus was not recognized until microbiologic culture results became available. Our case illustrates the importance of recognizing this fungus as an opportunistic infection in immunocompromised patients, as well as the need for culture of biopsy material for proper identification so that appropriate therapy can be instituted.
Cotyledonoid Leiomyoma
Authors: Cheuk W. , Chan John K. C. , Liu John Y. S.
Published: January 2021

Cotyledonoid leiomyoma or “grapelike” leiomyoma is a very rare tumor among the ever-expanding repertoire of growth variants described in benign uterine leiomyoma. We report a case of cotyledonoid leiomyoma in a 55-year-old woman who presented with menorrhagia and uterine prolapse. A large multinodular fungating tumor adhering to the right posterolateral wall of the uterus and extending to the broad ligament was discovered at vaginal hysterectomy. With a provisional diagnosis of sarcoma, total hysterectomy and bilateral salpingo-oophorectomy were performed. Postoperatively, the patient was well with no evidence of recurrence at 14 months. Pathologic examination revealed a 10-cm, red-brown tumor that comprised multiple bulbous processes protruding over the uterine surface, in continuity with a dissecting intramyometrial component. It was composed of fascicles and nodules of bland-looking smooth muscle cells with prominent perinodular hydropic degeneration. Coagulative necrosis, mitoses, and nuclear atypia were absent. Cotyledonoid leiomyoma apparently results from a combination of several uncommon growth patterns operating together, including subserosal growth, dissecting growth, and perinodular hydropic degeneration. Increased awareness of this grossly alarming variant of benign uterine leiomyoma can help avoid overtreatment.
Mental Tools for Thinking About DNA Technologies in New Ways
Authors: Root-Bernstein Robert , Root-Bernstein Michele
Published: January 2021

Objective.—To investigate the nature of creative thinking in biomedical science with specific applications to molecular pathologies and DNA technologies.

Data Sources.—Accounts of breakthroughs and inventions contained in autobiographies, biographies, interviews, and archival sources.

Study Selection.—Discoveries that have altered, or may yet alter, basic textbook accounts of biomedical sciences for which appropriate data sources exist.

Data Extraction.—Approximately 1000 data sources were analyzed, both within appropriate sciences and in other creative fields, such as the arts.

Data Synthesis.—The current analysis is based on a framework described in our previous book, Sparks of Genius, which outlines a general approach to understanding creative thinking.

Conclusions.—Creative thinking in all disciplines depends on a common mental “toolkit” that consists of 13 fundamental tools: observing, imaging, abstracting, pattern recognition, pattern forming, analogizing, body thinking, empathizing, dimensional thinking, modeling, playing, transforming, and synthesizing. Scientists recognize and solve problems by observing data that break the patterns established by theories; exploring a system by creating an abstract model with which they can play; and transforming data into feelings, sounds, and other forms that create surprising analogies to already-understood principles. The result of such personal thinking is knowledge combined with sensation and emotion—feeling and understanding synthesized into complete awareness. We illustrate some of these modes of thinking with reference to recent breakthroughs in DNA-related areas and suggest ways in which the use of “tools for thinking” can increase the probability of making further discoveries in the biomedical sciences.
Multiple Myeloma in Association With Sarcoidosis
Authors: Şen Filiz , Mann Karen P. , Medeiros L. Jeffrey
Published: January 2021

The association of sarcoidosis with Hodgkin disease and non-Hodgkin lymphoma is well known. However, multiple myeloma also can occur rarely in association with sarcoidosis. We describe a patient with sarcoidosis who subsequently developed multiple myeloma. The patient was a 49-year-old woman with a 4-year history of severe, chronic, active sarcoidosis involving her lungs, lymph nodes, eyes, and bone marrow. During the initial clinical workup, a serum monoclonal paraprotein was detected and bone marrow examination revealed a slight increase in plasma cells (4%), in addition to noncaseating granulomas. Thus, the diagnoses of monoclonal gammopathy of undetermined significance and sarcoidosis were established simultaneously. She sought medical attention for her current illness when she developed low back pain and weakness of her lower extremities. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin (Ig) G κ type, and quantification revealed an IgG level of 46.67 g/L (normal, 5.88–15.73 g/L). Bone marrow aspiration and biopsy revealed multiple myeloma and sarcoidosis. Including this patient, 11 cases of sarcoidosis and multiple myeloma have been reported to date, including 3 patients with monoclonal gammopathy of undetermined significance preceding the onset of multiple myeloma. In this case, as in most of the cases reported previously, sarcoidosis preceded the development of multiple myeloma.
Estimation of Size of Clonal Unit for Keratinocytes in Normal Human Skin
Authors: Chaturvedi Vijaya , Chu Sue , Carrol Mathew , Brenner Jennifer W. , Nickoloff Brian J.
Published: January 2021

Objective.—It has been suggested that keratinocyte (KC) stem cells reside at the epicenter of a clonal population of cells. To estimate the territory or surface area covered by a single stem-cell–derived KC population in human skin, clonal skin maps were created from 3 healthy adult women and from normal skin of a psoriatic patient.

Design.—Two hundred fifty-eight punch biopsy samples of various sizes (ranging from 2 to 8 mm in diameter) were analyzed for clonality employing X chromosome inactivation patterns at the human androgen receptor gene (HUMARA) locus. DNA was isolated and clonality established by significant decrease of either maternal or paternal X chromosome band patterns following restriction enzyme digestion, polymerase chain reaction amplification, and gel electrophoresis.

Results.—Fifty-three (41%) of 128 two-mm biopsies were clonal, whereas only 6 (14%) of 43 three-mm, 5 (14%) of 36 four-mm, and 3 (8%) of 35 five-mm biopsies revealed a clonal population of KCs. By contrast, in 5 different biopsies from a psoriatic patient, including 4- or 5-mm sizes, all but 1 were clonal; even an 8-mm biopsy contained a clonal population of KCs. Mantel-Haenszel χ2 analysis revealed a P value of .001, reflecting a strong trend in probability for presence of a single clone of KCs as related to size of the biopsy sample. By sequentially analyzing 30 contiguous 2-mm biopsy samples within a given strip of skin, 10 clonal domain changes, as reflected in maternal versus paternal switches, were observed.

Conclusions.—These results provide direct evidence of a clonal population of KCs in normal and psoriatic lesion-free skin, and indicate that a clonal epidermal unit of KCs frequently can be detected in small biopsies (2 mm), but that in normal skin sampling, overlapping clones are apparently present in larger (ie, 4–5-mm) biopsies, producing nonclonal patterns. The clonal domain of progeny in normal skin has a rather limited territorial boundary (2 mm in diameter). However, in lesion-free skin from a psoriatic patient, there may be clonal expansion of KCs due to perturbation in epidermopoiesis and/or stem cell distribution.
p53 Protein Overexpression in Bone Marrow Biopsies of Patients With Shwachman-Diamond Syndrome Has a Prevalence Similar to That of Patients With Refractory Anemia
Authors: Elghetany M. Tarek , Alter Blanche P.
Published: January 2021

Context.—Shwachman-Diamond syndrome (SDS) is a rare inherited disorder characterized by pancreatic insufficiency, neutropenia, and in some patients, metaphyseal dysostosis. Patients with SDS are at a high risk for development of bone marrow failure, myelodysplastic syndrome, and acute leukemia. The p53 gene plays a major role in cell-cycle regulation, particularly in the presence of a genetic alteration in DNA, a critical step for the initiation of leukemogenesis. p53 gene up-regulation and p53 protein overexpression may occur as a cellular reaction to significant DNA damage. Shwachman-Diamond syndrome and refractory anemia patients have close similarities in the prevalence of acute leukemia and in cell-cycle changes in bone marrow cells. This similarity was further investigated for p53 protein overexpression using archived tissue from patients with hematologic diseases having various leukemic propensities, including SDS and refractory anemia.

Methods.—Immunohistochemical staining for p53 protein overexpression was performed on bone marrow biopsies from 9 patients with SDS. These specimens were compared with biopsies from 71 patients with acquired hematologic disorders with variable risk levels for leukemia, including acquired aplastic anemia (n = 14), refractory anemia (n = 46), and various acquired cytopenias (n = 11), as well as 37 control subjects.

Results.—p53 protein overexpression was identified only in patients with SDS and in patients with refractory anemia; these groups exhibited comparable prevalences of 78% and 72%, respectively. None of the patients with acquired aplastic anemia, acquired cytopenias, or in the control group showed overexpression of p53 protein.

Conclusion.—The prevalence of p53 protein overexpression in SDS is significantly different from that in acquired aplastic anemia and acquired cytopenias, but it is similar to the prevalence in refractory anemia. We speculate that p53 protein overexpression in this bone marrow failure syndrome may represent an early indicator of significant DNA genetic alteration, which is a crucial step in the process of leukemogenesis.
Validation of p53 Immunohistochemistry as a Prognostic Factor in Breast Cancer in Clinical Practice
Authors: Bartley Angela N. , Ross Dennis W.
Published: January 2021

Context.—Abnormal p53 tumor suppressor gene expression as detected by immunohistochemistry is a possible prognostic factor in breast cancer. The difference in techniques used to evaluate the expression of mutated p53 protein is under intense scrutiny, as well as its uses either independently or in conjunction with other prognostic factors in breast cancer.

Objective.—To determine whether p53 immunohistochemistry can be used as a reliable indicator of the presence of mutated nuclear p53 protein, and whether this method can be performed reliably in a community hospital's clinical practice.

Design.—One hundred twenty-two cases of breast carcinoma were stained and analyzed for the presence of p53 protein using DO-7 (Dako Corporation, Carpinteria, Calif) p53 antibody.

Results.—Of the 122 cases of invasive carcinoma studied, 23 (18.7%) were positive for p53, and 16 (16.3%) of 98 cases with coexisting ductal carcinoma in situ were positive for p53. This finding is in agreement with comparable published studies.

Conclusions.—Based on the results of this study, we conclude that p53 immunohistochemistry qualifies as a diagnostic technique suitable for clinical practice in a community hospital. Its detection may be particularly promising in clinical trials of new molecular therapies directed at the p53 tumor suppressor gene.
Gastric Endocrine Pancreatic Heterotopia
Authors: Hammock Lauren , Jorda Merce
Published: January 2021

Heterotopic pancreas is a relatively infrequent lesion most often found in the stomach. Four histologic types are recognized: total, canalicular, exocrine, and endocrine heterotopia. To our knowledge, only 2 cases of purely endocrine heterotopic pancreas have been reported in detail. We describe the case of a patient with gastric and duodenal ulcers and gastric endocrine heterotopia. The lack of mass formation, histomorphology, and immunohistochemical features simulating islets of Langerhans supported the diagnosis. We conclude that purely endocrine heterotopic pancreas is a very rare entity that, when present, can simulate a primary or metastatic neuroendocrine tumor. Adequate sampling of the specimen, histomorphologic pattern, and immunohistochemistry are important for the purpose of distinguishing between a neuroendocrine tumor and purely endocrine pancreatic heterotopia.
Transient Myeloproliferative Disorder With Erythroid Differentiation in Down Syndrome
Authors: Bozner Peter
Published: January 2021

A newborn with a karyotype of 47, XY, +21 presented at birth with a white blood cell count of 27 700/μL of which 61% were blast cells. The blast cell morphologic structure was initially not characteristic of any particular lineage, although the cytoplasm contained fine granules and occasional small vacuoles. Routine cytochemical stains were negative, except one for nonspecific esterase that was faintly positive in most of the blast cells. Flow cytometric analyses showed that the blast cells expressed glycophorin A with a subset dimly coexpressing CD45 and were negative for CD34, CD71, myeloid, lymphoid, and platelet-associated antigens. These immunophenotypic findings were consistent with an abnormal erythroid phenotype. A few days postpartum, markedly dysplastic erythroid precursor cells appeared in the peripheral blood and increased in number as the early blast cells decreased. After a period of subdued blast cell production, a second wave of increase in the number of blast cells and dysplastic erythroblasts followed and ended with the disappearance of circulating abnormal cells. The child is now 5 years old and no major illness has been reported since the remission of this disorder. This case most likely belongs to the category of transient myeloproliferative disorders, although the erythroid-like phenotype of blast cells and the evidence of single-lineage maturation to circulating dysplastic erythroid precursors allow the suggestion that this process could represent a special form of a self-limited hematologic disorder in Down syndrome.
Fine-Needle Aspiration of Renal Angiosarcoma
Authors: Johnson Viviana V. , Gaertner Erich M. , Crothers Barbara A.
Published: January 2021

Angiosarcoma of the kidney is an unusual neoplasm, and primary renal angiosarcoma is exceedingly rare, with fewer than 11 well-documented cases reported to date. To our knowledge, no publication to date has correlated the fine-needle aspiration cytologic findings in renal angiosarcoma with the gross, histologic, and immunohistochemical findings. A 50-year-old man presented with a left kidney mass and multiple liver and pulmonary nodules. Computed tomography–guided fine-needle aspiration biopsies of the renal mass and a hepatic nodule were performed and demonstrated malignant spindle cells consistent with angiosarcoma. The diagnosis was confirmed at autopsy through histologic examination and associated ancillary studies. This case presents the fine-needle aspiration cytologic findings in renal angiosarcoma and correlates these findings with the gross pathologic, histologic, and immunohistochemical findings.
Malignant Stromal Tumor of the Gallbladder With Interstitial Cells of Cajal Phenotype
Authors: Mendoza-Marin Marisela , Hoang Mai P. , Albores-Saavedra Jorge
Published: January 2021

Malignant mesenchymal tumors of the gallbladder are exceedingly rare. We report a malignant stromal tumor of the gallbladder with a phenotype of interstitial cells of Cajal. To our knowledge, only the benign counterpart of this tumor has been described previously. A 34-year-old woman presented with right upper quadrant abdominal pain. At the time of cholecystectomy, the gallbladder was noted to have a thickened wall and a polypoid mass arising in the neck of the gallbladder. Histologic sections showed a cellular proliferation of spindle neoplastic cells that were arranged in short fascicles. Numerous mitotic figures and foci of necrosis were noted. The neoplastic cells expressed CD117 (c-Kit protein) and vimentin. They were negative for smooth muscle actin, desmin, myoglobin, cytokeratin, S100 protein, and CD34. Our case demonstrates that a malignant stromal tumor that is histologically and immunohistochemically identical to gastrointestinal stromal tumor can occur in the gallbladder, and that the expression of CD117 may be of therapeutic importance.
Laboratory Diagnosis of Dysfibrinogenemia
Authors: Cunningham Mark T. , Brandt John T. , Laposata Michael , Olson John D.
Published: January 2021

Dysfibrinogenemia is a coagulation disorder caused by a variety of structural abnormalities in the fibrinogen molecule that result in abnormal fibrinogen function. It can be inherited or acquired. The inherited form is associated with increased risk of bleeding, thrombosis, or both in the same patient or family. Traditionally, dysfibrinogenemia is diagnosed by abnormal tests of fibrin clot formation; the thrombin time and reptilase time are the screening tests, and the fibrinogen clotting activity–antigen ratio is the confirmatory test. The inherited form is diagnosed by demonstrating similar laboratory test abnormalities in family members, and if necessary by analysis of the fibrinogen protein or fibrinogen genes in the patient. The acquired form is diagnosed by demonstrating abnormal liver function tests and by ruling out dysfibrinogenemia in family members. This article reviews the laboratory testing of dysfibrinogenemia and presents an algorithm for sequential test selection that can be used for diagnosis.
Malignant Eccrine Spiradenoma
Authors: Mirza Imran , Kloss Robert , Sieber Steven C.
Published: January 2021

Malignant transformation of eccrine spiradenoma is extremely rare. We describe the case of a 70-year-old man with malignant eccrine spiradenoma of the forearm and metastases to the axillary lymph nodes. Surgical excision with adequate margins and lymph node dissection was performed. Tamoxifen therapy was instituted after obtaining positive immunostaining results for estrogen receptor. After 41 months of follow-up, there has been no recurrence or distant metastases. Wide local excision and close follow-up are crucial in the management of malignant eccrine spiradenoma. The role of other therapeutic modalities, including hormonal therapy, remains to be determined.
Oncocytoma-like Angiomyolipoma
Authors: Martignoni Guido , Pea Maurizio , Bonetti Franco , Brunelli Matteo , Eble John N.
Published: January 2021

We report the clinical, pathologic, and immunohistochemical features of an unusual tumor of the kidney composed of densely eosinophilic, polygonal epithelioid cells. The patients were a 56-year-old woman and a 35-year-old man. The renal tumors were discovered during follow-up for breast carcinoma and evaluation for abdominal pain, respectively. The tumors closely resembled oncocytoma in routine sections, but were negative for epithelial markers and positive for HMB-45, a pattern of reactions characteristic of angiomyolipoma. In the woman, a single additional microscopic angiomyolipoma was present in the renal parenchyma at a distance from the main tumor. Both patients are alive without recurrence 7 and 10 years after surgery, respectively. Based on clinical, morphologic, and immunophenotypic features, we conclude that these tumors are oncocytoma-like angiomyolipomas.
Primary Salivary Clear Cell Tumors—A Diagnostic Approach
Authors: Wang Beverly , Brandwein Margaret , Gordon Ronald , Robinson Robert , Urken Mark , Zarbo Richard J.
Published: January 2021

Context.—Primary salivary clear cell tumors comprise an uncommonly encountered subgroup of salivary neoplasia. We hypothesize that clear cell carcinoma does not represent a “monomorphic” variant of epithelial-myoepithelial carcinoma, but is distinct in terms of histogenesis and tumor biology.

Objectives.—To compare the clinicopathologic features of 20 cases of salivary primary clear cell tumors, including 12 clear cell carcinomas (CCCs), 7 epithelial-myoepithelial carcinomas (EMECs), and 1 clear cell myoepithelial carcinoma (CCMEC); to investigate their interrelationship with regard to myoepithelial differentiation; and to offer a diagnostic approach for distinguishing between these entities.

Design.—Retrospective and prospective identification and review of patients diagnosed with primary salivary clear cell neoplasia and review of the English language literature.

Setting.—Three academic tertiary-care hospitals.

Patients.—We identified 12 patients with CCC, 7 with EMEC, and 1 with CCMEC. Patients included 11 men and 9 women, aged 30 to 88 years (median 72.5 years).

Main Outcomes Measures.—Immunohistochemical reactivity for S100, muscle-specific actin, and calponin; ultrastructural examination when feasible; review of patient charts; and telephone interviews to establish clinical outcome.

Results.—Clear cell carcinoma has a predilection for intraoral sites, whereas EMEC has a predilection for the parotid. All 3 of the tumor types studied have a propensity for locoregional recurrence, which can manifest decades after initial surgery. There were no mortalities among patients with CCC, even after pulmonary metastasis in 2 patients, confirming the indolent nature of this group of clear cell tumors. A meta-analysis of reported cases of CCC, EMEC, and CCMEC confirmed that EMEC and CCMEC have a much greater propensity for locoregional recurrence than CCC, despite the predilection of both for a more surgically accessible site (parotid). We found no definitive evidence of myoepithelial differentiation in CCC, indicating that it is probably morphogenetically distinct from EMEC and CCMEC, both tumors with diagnostically requisite myoepithelial differentiation.

Conclusions.—The initial treatment of choice for CCC, CCMEC, and EMEC is surgical resection with negative margins. Locoregional recurrence should be treated aggressively, as it is still consistent with long disease-free intervals. The lack of myoepithelial differentiation in CCC is consistent with the concept that this tumor is histomorphogenically distinct from EMEC and that it is not merely a monomorphic variant.
Evaluation of the Tissue Microarray Technique for Immunohistochemical Analysis in Rectal Cancer
Authors: Fernebro Eva , Dictor Michael , Bendahl Pär-Ola , Fernö Mårten , Nilbert Mef
Published: January 2021

Background.—Immunohistochemical staining for tumor-associated proteins is widely used for the identification of novel prognostic markers. Recently, a tissue-conserving, high-throughput technique, tissue microarray, has been introduced. This technique uses 0.6-mm tissue core biopsy specimens, 500 to 1000 of which are brought into a new paraffin array block, which can be sectioned up to 100 times.

Methods.—We evaluated the tissue microarray technique for immunohistochemical analysis in 20 rectal cancers. Immunohistochemical staining was performed for the proliferation marker Ki-67 and the tumor suppressor protein p53 in whole tissue sections and in tissue core biopsy specimens.

Results.—The whole tissue sections were assessed by counting all cells in 10 high-power fields (×40), which resulted in a mean fraction of Ki-67–expressing tumor cells of 0.81 (range, 0.54–1.0). p53 expression assessed in whole tissue sections showed nuclear staining in 15 (75%) of 20 rectal carcinomas. For the tissue microarray technique, a median of 3 (range, 3–5) 0.6-mm tissue core biopsy specimens were studied from each of the 20 tumor specimens. The tissue microarray method gave a mean Ki-67 expression of 0.85 (range, 0.50–1.0) in tumor cell nuclei and showed p53 protein expression in the same 15 of 20 tumors as in the whole tissue sections.

Conclusion.—We conclude that the tissue microarray technique for immunohistochemical staining in rectal cancer yields staining of good quality and expression data for Ki-67 and p53 comparable to those obtained with whole tissue staining. The feasibility of tissue microarray thus enables time- and tissue-preserving studies of multiple markers in large tumor series.
Discrepancy in Pathologic Diagnosis of Placental Lesions
Authors: Sun Chen-Chih J. , Revell Vania O. , Belli Anthony J. , Viscardi Rose M.
Published: January 2021

Context.—Placentas are routinely examined by surgical pathologists, but peer review of placental diagnosis is rarely performed.

Objective.—To determine the frequency of discrepant placental diagnosis between general surgical pathologists and a pediatric pathologist.

Design.—One hundred fourteen placentas from infants with intrauterine growth restriction (IUGR) and 170 placentas from infants appropriate for gestational age (AGA) were reviewed for 10 lesion types using standardized criteria. The review diagnosis was compared with original reports.

Results.—The review identified 333 lesions, 168 in the IUGR group and 165 in AGA group. Discrepant diagnosis occurred in 137 lesions (41.1%). There was no significant difference in the frequency of discrepant diagnosis between the IUGR (44.7%) and AGA groups (37.6%) (P > .05). Most discrepancies (92.7%) were due to underdiagnosis (identified on review but not mentioned in original diagnosis), but a few (7.3%) were due to misdiagnosis (mentioned in original report but disagreed on review). The common underdiagnoses with their corresponding rates were as follows: hemorrhagic endovasculitis (84.6%), fetal thrombotic vasculopathy (75%), massive perivillous fibrin deposition (68.4%), maternal floor infarction (66.7%), retroplacental hemorrhage (60.6%), intervillous thrombus (57.1%), decidual angiopathy (33.3%), placental infarction (25.4%), acute chorioamnionitis (22.7%), and chronic villitis (21.7%). Misdiagnosis was found in 10 cases: 5 cases of infarction (review diagnosis was perivillous fibrin deposits in 4, intervillous thrombus in 1), 3 cases of acute chorioamnionitis, and 2 cases of decidual angiopathy. Among the 8 general surgical pathologists involved, the frequency of discrepant diagnosis ranged from 31.5% to 58.6% (P > .05). The intraobserver discrepancy rate for the reviewer was 4.8%, significantly lower than the discrepancy rate for the 8 general surgical pathologists.

Conclusion.—It is common for general surgical pathologists not to recognize placental lesions, which may have clinical significance. Awareness of this deficiency, standardization of diagnostic criteria, and increased knowledge in placental pathology may improve the quality of diagnosis in this area.
Continuous Wristband Monitoring Over 2 Years Decreases Identification Errors
Authors: Howanitz Peter J. , Renner Stephen W. , Walsh Molly K.
Published: January 2021

Context.—Identification of patients is one of the first steps in ensuring the accuracy of laboratory results. In the United States, hospitalized patients wear wristbands to aid in their identification, but wristbands errors are frequently found.

Objective.—To investigate if continuous monitoring of wristband errors by participants of the College of American Pathologists (CAP) Q-Tracks program results in lower wristband error rates.

Setting.—A total of 217 institutions voluntarily participating in the CAP Q-Tracks interlaboratory quality improvement program in 1999 and 2000.

Design.—Participants completed a demographic form, answered a questionnaire, collected wristband data, and at the end of the year, best and most improved performers answered another questionnaire seeking suggestions for improvement. Each institution's phlebotomists inspected wristbands for errors before performing phlebotomy and recorded the number of patients with wristband errors. On a monthly basis, participants submitted data to the CAP for data processing, and at the end of each quarter, participants received summarized comparisons. At the end of each year, participants also received a critique of the results along with suggestions for improvement.

Main Outcome Measures.—The percentage of wristband errors by quarter, types of wristband errors, and suggestions for improvement.

Results.—During 2 years, 1 757 730 wristbands were examined, and 45 197 wristband errors were found. The participants' mean wristband error rate for the first quarter in 1999 was 7.40%; by the eighth quarter, the mean wristband error rate had fallen to 3.05% (P < .001). Continuous improvement occurred in each quarter for participants in the 1999 and 2000 program and in 7 of 8 quarters for those who participated in both 1999 and 2000. Missing wristbands accounted for 71.6% of wristband errors, and best performers usually had wristband error rates under 1.0%. The suggestion for improvement provided by the largest number of best and most improved performers was that phlebotomists should refuse to perform phlebotomy on a patient when a wristband error is detected.

Conclusions.—The wristband error rate decreased markedly when this rate was monitored continuously using the CAP Q-Tracks program. The Q-Tracks program provides a useful tool for improving the quality of services in anatomic pathology and laboratory medicine.
A Carcinosarcoma/Sarcomatoid Carcinoma Arising in a Urinary Bladder Diverticulum
Authors: Omeroglu Atilla , Paner Gladell P. , Wojcik Eva M. , Siziopikou Kalliopi
Published: January 2021

We describe an invasive polypoid carcinosarcoma/sarcomatoid carcinoma arising within a urinary bladder diverticulum in a 65-year-old patient with synchronous, moderately differentiated prostatic adenocarcinoma. Histologically, the diverticular tumor exhibits an admixture of different morphologic components, including invasive high-grade urothelial carcinoma, malignant glandular structures in a cellular background of malignant spindle cells, and areas formed exclusively by spindle and pleomorphic cells. There was full-thickness involvement of the diverticulum with extension of the tumor into the perivesical fat and ipsilateral seminal vesicle. In view of the early invasive behavior of carcinosarcoma/sarcomatoid carcinoma combined with the paucity of the muscular layer in the diverticulum wall, a graver prognosis was expected for this aggressive tumor that occurred in this unusual site.
Informed Consent and the Process of Cadaver Donation
Authors: Chung Christine S. , Lehmann Lisa Soleymani
Published: January 2021

Context.—Informed consent entails more than signing a document. Ideally, it should involve a process in which individuals are given sufficient information to make a voluntary decision. Little is known about the process of informed consent for cadaver donation.

Objective.—To assess existing consent procedures for cadaver donation in a sample of US medical schools.

Design.—Cross-sectional survey and content analysis of informational brochures and consent forms given to potential cadaver donors.

Setting and Participants.—The 22 largest medical schools in the United States, as ranked by the number of medical students in the Association of American Medical Colleges Institutional Profile System Annual Report 1995–1996.

Main Outcome Measures.—Description of dissection procedure, information provided about dissection, and the process for obtaining consent.

Results.—Of the 22 schools studied, 18 schools (82%) mentioned the altruistic nature of cadaver donation. Twenty-one schools (96%) specified that bodies would be used to teach students, and 16 schools (73%) specified that bodies would be used for research. One school (4%) noted that organs could be permanently preserved for teaching purposes. Only 2 schools (9%) provided any description of the dissection procedures to be performed on the cadavers. Seven schools (32%) used the term dissect at least once. None of the schools offered to provide a complete account of the dissection procedure.

Conclusions.—The existing consent procedures for cadaver donations at US medical schools do not provide sufficient information to potential donors to constitute a fully informed consent.
The Role of the Autopsy in Medical Malpractice Cases, I
Authors: Bove Kevin E. , Iery Clare
Published: January 2021

Context.—Fear that damaging information from autopsy may be introduced as evidence in lawsuits alleging medical malpractice is often cited as one factor contributing to the decline in autopsy rates.

Objective.—To determine how autopsy information influences the outcome of medical malpractice litigation.

Design.—We studied state court records in 99 cases of medical malpractice adjudicated from 1970 to the present to assess the role of information from autopsies in the outcomes.

Results.—The 3 largest groups defined by cause of death at autopsy were acute pulmonary embolism, acute cardiovascular disease, and drug overdose/interaction. Findings for defendant physicians outnumbered medical negligence in the original trial proceedings by a 3:1 margin. The appellate courts affirmed 51 acquittals and 19 findings of negligence, and reversed the original trial court decision in 29 cases for technical reasons. We found no significant relationship between accuracy of clinical diagnosis (using the autopsy standard) and outcome of a suit charging medical negligence. Even when a major discrepancy existed between the autopsy diagnosis and the clinical diagnosis, and the unrecognized condition was deemed treatable, defendant physicians were usually exonerated. Moreover, major diagnostic discrepancies were relatively uncommon in suits in which a physician was found to be negligent. Conversely, in about 20% of cases, autopsy findings were helpful to defendant physicians.

Conclusions.—Our study confirms that a finding of medical negligence is based on standard-of-care issues rather than accuracy of clinical diagnosis. Autopsy findings may appear to be neutral or favorable to either the plaintiff or the defendant, but are typically not the crux of a successful legal argument for either side in a malpractice action. We conclude that fear of autopsy findings has no rational basis and is an important obstacle to uninhibited outcomes analysis.