bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Esophageal Liposarcoma: A Case Report and Review of the Literature
Authors: Garcia Monica , Buitrago Efren , Bejarano Pablo A. , Casillas Javier
Published: February 2021

Liposarcoma is one of the most common neoplasms of adulthood. However, it is exceedingly rare in the gastrointestinal tract. To our knowledge, only 12 cases occurring in the esophagus have been reported in the world literature to date. We report the case of a 42-year-old man with a pleomorphic liposarcoma arising in the esophageal wall. The morphologic, immunophenotypic, and ultrastructural characteristics are presented, as well as the results of literature review.
Distinguishing Small Cell Carcinoma From Non–Small Cell Carcinoma of the Lung: Correlating Cytologic Features and Performance in the College of American Pathologists Non-Gynecologic Cytology Program
Authors: Renshaw Andrew A. , Voytek Theresa M. , Haja Jennifer , Wilbur David C.
Published: February 2021

Context.—The cytologic features of small cell carcinoma of the lung are well described. Nevertheless, some small cell carcinomas may be difficult to reproducibly distinguish from non–small cell carcinomas, and this distinction carries significant clinical importance.

Objective.—To correlate the cytologic features of individual cases of small cell carcinoma of the lung in fine-needle aspiration specimens from the College of American Pathologists Non-Gynecologic Peer Comparison Cytology Program with the frequency of misclassification as non– small cell carcinoma.

Design.—We reviewed 1185 interpretations of 23 different cases of small cell carcinoma in lung fine-needle aspiration specimens and correlated the cytologic features noted in these cases with performance in the program.

Results.—Cases were divided into those that were frequently misclassified as non–small cell carcinoma (at least 10% of the responses, 11 cases) and those that were infrequently misclassified as non–small cell carcinoma (<5% of all responses, 12 cases). All cases had areas on the slides with classic features of small cell carcinoma. However, 10 of 11 cases that were frequently misclassified as non–small cell carcinoma had cells with either increased cytoplasm (4 cases), cytoplasmic globules (so-called paranuclear blue bodies) (3 cases), or apparent intracytoplasmic lumina (3 cases). These features were not identified in cases that were infrequently misclassified (P = .005). In addition, cases more frequently misclassified as non–small cell carcinoma tended to show better overall cellular and group preservation.

Conclusions.—Frequent misclassification of small cell carcinoma as non–small cell carcinoma in lung fine-needle aspiration specimens in this program correlates strongly with the presence of cytoplasmic features that may suggest non–small cell carcinoma or with the presence of paranuclear blue bodies. Misclassification in this program may reflect a variety of factors, including the variation in the cytologic features of individual cases, but also the lack of wide recognition that some features of non–small cell carcinoma may also be noted in well-preserved cases of small cell carcinoma.
A Fast and Simple High-Performance Liquid Chromatography/Mass Spectrometry Method for Simultaneous Measurement of Whole Blood Tacrolimus and Sirolimus
Authors: Wang Sihe , Magill Jenny E. , Vicente Faye B.
Published: February 2021

Context.—Combined immunosuppressant therapy using tacrolimus and sirolimus has demonstrable benefits. Simultaneous chromatographic monitoring of whole blood tacrolimus and sirolimus is useful for reducing reagent consumption and turnaround time. We report here a simple and rapid method using high-performance liquid chromatography/mass spectrometry for simultaneous measurement of whole blood tacrolimus and sirolimus.

Objective.—To develop and validate a high-performance liquid chromatography/mass spectrometry method that is suitable for clinical laboratories and that is simple, rapid, and cost-effective.

Design.—Whole blood (80 μL) was mixed with zinc sulfate solution, followed by protein precipitation with acetonitrile containing the internal standards. After brief centrifugation, the supernatant (20 μL) was injected onto a C18 guard column. The drug and the internal standard ammonium adducts were monitored by multiple reaction monitoring. One-point calibration at levels of 200 ng/mL (249 nM) tacrolimus and 100 ng/mL (109 nM) sirolimus was prepared by adding tacrolimus and sirolimus to immunosuppressant-free whole blood.

Results.—The assay took 2.5 minutes per sample injection. The total imprecision was between 2.46% and 7.04% for tacrolimus and between 5.22% and 8.30% for sirolimus across the concentrations tested. No carryover was observed, and recoveries were 92% to 98% for tacrolimus and 100% for sirolimus at all levels tested. The tacrolimus was linear from 0.52 to 155.5 ng/mL (0.65–193.4 nM), and sirolimus was linear from 0.47 to 94.8 ng/mL (0.51–103.7 nM). Biases of correlations with commercial methods were within 7%.

Conclusions.—This improved method is simple, fast, cost-effective, and suitable for clinical laboratories. It has been implemented for routine clinical monitoring of posttransplantation immunosuppressant therapy.
Primary Breast Lymphoma Cytologic Diagnosis
Authors: Vardar Enver , Ozkok Guliz , Cetinel Mehtap , Postaci Hakan
Published: February 2021

Primary non-Hodgkin lymphoma of the breast is a rare pathology, and bilateral involvement is exceptional. We report a case of bilateral primary non-Hodgkin lymphoma of the breast in a 40-year-old woman. Predominantly atypical lymphocytes and rare plasma cells were found in the microscopic evaluation of the fine-needle aspiration biopsy of the right and left breasts. Microscopic findings of the incisional biopsy of the left breast were in accordance with non-Hodgkin diffuse large B-cell lymphoma. The patient received systemic chemotherapy and is alive with no evidence of recurrence for 2 years.
Monophasic Synovial Sarcoma of the Liver
Authors: Srivastava Amitabh , Nielsen Petur G. , Cin Paola Dal , Rosenberg Andrew E.
Published: February 2021

We report a hepatic monophasic synovial sarcoma in a 60-year-old woman who presented with right upper quadrant pain subsequent to an intrahepatic bleed from a highly vascular tumor mass. Imaging studies showed a dominant tumor mass in the right hepatic lobe with multiple satellite nodules. A detailed physical examination and radiologic workup failed to reveal a primary tumor elsewhere. A right partial hepatectomy was performed with a preoperative differential diagnosis of angiosarcoma versus hepatocellular carcinoma. The morphologic, immunophenotypic, and cytogenetic findings (t(X;18)(p11.2;icq11.2)) were consistent with a monophasic synovial sarcoma. Postoperative clinical evaluation of the extremities and a positron emission tomographic scan performed 4 weeks after surgery showed no evidence of recurrent or metastatic disease. The patient was started on an aggressive 4-drug chemotherapy regimen, but died 3 months thereafter from widespread metastatic disease. No autopsy was performed. The presence of multiple lesions in the liver certainly suggests the possibility of metastatic disease. It would, however, be very unusual for a synovial sarcoma to present as an occult primary, and the negative radiologic workup 1 month after the partial hepatectomy also argues against this possibility. The clinical presentation, radiographic findings, and subsequent course in this patient was therefore most consistent with a primary monophasic synovial sarcoma of the liver.
Small Lymphocytic Lymphoma Involving an Enlarging Complex Renal Cyst
Authors: Iczkowski Kenneth A. , Gapin Tracy B. , Wajsman Zev
Published: February 2021

A 47-year-old white man presented for evaluation of a complex right renal mass. He had a history of human immunodeficiency virus. Cervical lymph node biopsy had revealed small lymphocytic lymphoma. Computed tomographic scan disclosed diffuse mesenteric and retroperitoneal adenopathy consistent with chronic lymphocytic leukemia, as well as a 4.5-cm complex cystic right renal mass, which 17 months later enlarged to 6.2 cm. The mass resembled multiloculated cystic nephroma. Partial nephrectomy revealed infiltration of the cyst wall by small lymphocytic lymphoma. To our knowledge, this is the first reported case of lymphoma arising in or colonizing a renal cyst.
Adrenocortical Tumors in Brazilian Children: Immunohistochemical Markers and Prognostic Factors
Authors: Sbragia Lourenco , Oliveira-Filho Antonio Goncalves , Vassallo Jose , Pinto Glauce Aparecida , Guerra-Junior Gil , Bustorff-Silva Joaquim
Published: February 2021

Context.—The behavior of adrenocortical tumors (ACTs) is usually difficult to establish in childhood, and the role of immunomarkers in predicting outcome has not yet been elucidated.

Objective.—To investigate the relationship between clinical, pathologic, and immunohistochemical findings and prognosis in a series of children with ACTs.

Patients and Methods.—Clinical data were evaluated retrospectively in 33 children with ACTs, including age at diagnosis, sex, time between first symptoms and diagnosis, clinical signs and symptoms, tumor position, and follow-up. Histologic sections were reviewed, each tumor was classified, and staging was performed according to previously published criteria. Immunohistochemical analysis of p53, Ki-67, c-Erb-B2, and Bcl-2 was performed according to previously published techniques.

Results.—Sixty-four percent (n = 21) of the patients were female, and the age at diagnosis in the cohort ranged from 2 to 96 months. Virilization alone affected 70% (n = 23) of the patients, and 18 patients had stage 1 disease, 9 had stage 2 disease, and 3 each had stage 3 and stage 4 disease. Female sex and stage 1 and stage 2 disease were associated with good outcome. None of the histopathologic criteria evaluated correctly predicted outcome. Only tumors with a volume exceeding 200 mL were associated with malignant behavior. Because only a small number of tumors expressed the antigens, results of these immunohistochemical tests were considered inconclusive.

Conclusion.—In this sample of pediatric ACTs, the clinical and surgical parameters are the most important prognostic factors, while the immunohistochemical markers evaluated were not predictive of outcome.
Frozen Section of Skin Specimens
Authors: Smith-Zagone Megan J. , Schwartz Mary R.
Published: February 2021

Context.—Skin cancers are the most common malignancies in this country. Treatment of these tumors often involves assessment of margins, which may be performed by frozen section.

Objective.—This article discusses indications for frozen section, various approaches to gross examination of specimens, Mohs micrographic surgery, diagnostic pitfalls, methods to improve diagnostic accuracy, and special techniques.

Data Sources.—The authors' extensive experience and review of the published literature.

Conclusions.—Frozen sections play a vital role in the evaluation of margins of basal cell carcinomas and squamous cell carcinomas. The role of frozen sections in evaluation of soft tissue tumors is controversial. With rare exception, they have no role in the evaluation of melanocytic tumors.
Intraoperative Consultation in Gynecologic Pathology
Authors: Coffey Donna , Kaplan Alan L. , Ramzy Ibrahim
Published: February 2021

Context.—Gynecologic specimens are commonly submitted for intraoperative consultation, primarily to confirm the presence and histologic type of malignancy, as well as to determine the adequacy of resection by examining the surgical margins.

Objective.—To review and discuss the application, indications, contraindications, and limitations of intraoperative consultation regarding gynecologic specimens, as well as the causes of false-positive or false-negative frozen section results.

Data Sources.—Review of the pertinent literature and the authors' expertise and experience.

Conclusions.—In most instances, intraoperative consultation regarding gynecologic specimens accurately determines the type of malignancy, the status of the resection margins or the lymph nodes, and the extent and depth of involvement by a tumor. Although the pathologist and the surgeon must be aware of the limitations, the use of intraoperative consultation represents a highly sensitive and specific technique that can play a critical role in the management of gynecologic disease.
Frozen Section of Thyroid and Parathyroid Specimens
Authors: Anton Rose C. , Wheeler Thomas M.
Published: February 2021

Context.—Preoperative fine-needle aspiration of thyroid lesions has greatly diminished the need for surgical evaluation. However, because thyroid nodules are common lesions, many still require surgical intervention and represent a substantial number of cases that the pathologist encounters in the frozen section laboratory.

Objective.—Comprehensive reviews of frozen section indications, as well as gross, cytologic, and histologic features of the most common and diagnostically important thyroid and parathyroid lesions, are presented to provide a guideline for proper triage and management of these cases in the frozen section laboratory. The most common pitfalls are discussed in an attempt to avoid discordant diagnoses.

Data Sources.—Thyroid lobectomy, subtotal or total thyroidectomy, and parathyroid biopsy or parathyroidectomy cases are included in this review.

Conclusions.—The frozen section evaluation of thyroid and parathyroid lesions remains a highly accurate procedure with a low false-positive rate. Gross inspection, complemented by cytologic and histologic review, provides the surgeon with the rapid, reliable, cost-effective information necessary for optimum patient care.
Analytic Bias of Thyroid Function Tests: Analysis of a College of American Pathologists Fresh Frozen Serum Pool by 3900 Clinical Laboratories
Authors: Steele Bernard W. , Wang Edward , Klee George G. , Thienpont Linda M. , Soldin Steven J. , Sokoll Lori J. , Winter William E. , Fuhrman Susan A. , Elin Ronald J.
Published: February 2021

Context.—In proficiency testing surveys, there are differences in the values reported by users of various analytic methods. Two contributors to this variation are calibrator bias and matrix effects of proficiency testing materials.

Objectives.—(1) To quantify the biases of the analytic methods used to measure thyroid-stimulating hormone, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels; (2) to determine if these biases are within allowable limits; and (3) to ascertain if proficiency testing materials correctly identify these biases.

Design.—A fresh frozen serum specimen was mailed as part of the 2003 College of American Pathologists Ligand and Chemistry surveys. The means and SDs for each analytic method were determined for this sample as well as for a proficiency testing sample from both surveys. In the fresh frozen serum sample, target values for thyroxine and triiodothyronine were determined by isotope dilution/liquid chromatography/tandem mass spectrometry. All other target values in the study were the median of the means obtained for the various analytic methods.

Main Outcome Measures.—Calibration biases were calculated by comparing the mean of each analytic method with the appropriate target values. These biases were evaluated against limits based on intra- and interindividual biological variation. Matrix effects of proficiency testing materials were assessed by comparing the rank of highest to lowest analytic method means (Spearman rank test) for each analyte.

Participants.—Approximately 3900 clinical laboratories were enrolled in the College of American Pathologists Chemistry and Ligand surveys.

Results.—The number of methods in the Ligand Survey that failed to meet the goals for bias was 7 of 17 for thyroid-stimulating hormone and 11 of 13 for free thyroxine. The failure rates were 12 of 16 methods for thyroxine, 8 of 11 for triiodothyronine, and 9 of 11 for free triiodothyronine. The means of the analytic method for the proficiency testing material correlated significantly (P < .05) only with the fresh frozen serum means for thyroxine and thyroid-stimulating hormone in the Chemistry Survey and free triiodothyronine in the Ligand Survey.

Conclusions.—A majority of the methods used in thyroid function testing have biases that limit their clinical utility. Traditional proficiency testing materials do not adequately reflect these biases.
Utility of Immunohistochemistry in Distinguishing Primary Adenocarcinomas From Metastatic Breast Carcinomas in the Gastrointestinal Tract
Authors: O'Connell Fionnuala P. , Wang Helen H. , Odze Robert D.
Published: February 2021

Context.—Breast carcinoma often metastasizes to the gastrointestinal tract, especially the stomach, where it is frequently difficult to distinguish from a primary gastric carcinoma.

Objective.—To evaluate the utility of immunohistochemical stains in differentiating primary gastric carcinomas from metastatic breast carcinomas.

Design.—Mucosal biopsy specimens from 47 adenocarcinomas involving the gastrointestinal tract (28 primary gastric carcinomas and 19 metastatic breast carcinomas) and 16 control cases of primary breast carcinomas without metastasis were immunohistochemically stained for estrogen receptor protein (ER), progesterone receptor protein (PR), gross cystic disease fluid protein (GCDFP), human epidermal growth factor receptor 2 protein, cytokeratin (CK) 5/6, CK/7, CK/20, a panel of mucin glycoprotein antigens (MUC2, MUC3, MUC5AC, and MUC6), monoclonal antibody DAS-1, and caudal-type homeobox transcription factor CDX2 and compared between primary and metastatic adenocarcinomas.

Results.—Highly significant proportions of metastatic breast carcinomas were positive for ER (72%), PR (33%), GCDFP (78%), and CK5/6 (61%) compared with primary gastric carcinomas (ER, 0%; PR, 0%; GCDFP, 0%; and CK5/6, 14%) (P < .001, P = .002, P < .001, and P = .004, respectively). Of these immunostains, ER, PR, and GCDFP were 100% specific. Primary breast tumors and their metastases showed a similar phenotypic profile. In contrast, primary gastric carcinomas showed significantly higher proportions of cases that stained with CK20 (50%), MUC2 (54%), MUC5AC (71%), MUC6 (39%), DAS-1 (43%), and CDX2 (67%) compared with metastatic breast carcinomas (CK20, 0%; MUC2, 24%; MUC5AC, 6%; MUC6, 0%; DAS-1, 0%; and CDX2, 0%) (P = .001, P = .01, P < .001, P = .02, P = .009, and P < .001, respectively). No significant differences were observed with regard to any of the other immunostains (human epidermal growth factor receptor 2 protein, CK7, and MUC3) between the patient groups.

Conclusions.—Estrogen receptor protein, PR, GCDFP, CK5/6, CK20, MUC5AC, MUC6, DAS-1, and CDX2 are helpful in distinguishing primary gastric carcinomas from metastatic breast carcinomas. Of these, ER, PR, and GCDFP are highly specific for metastatic breast carcinomas, whereas CK20, DAS-1, MUC2, MUC5AC, MUC6, and CDX2 are highly specific for primary gastric carcinomas.
Dendriform Pulmonary Ossification, a Form of Diffuse Pulmonary Ossification: Report of a 26-Year Autopsy Experience
Authors: Lara Jonathan F. , Catroppo James F. , Kim Dae U. , Costa Delineda
Published: February 2021

Context.—Dendriform pulmonary ossification (DPO) is an uncommon form of diffuse pulmonary ossification that typically affects the pulmonary interstitium in a setting of interstitial fibrosis.

Objective.—To determine the incidence and characteristics of DPO and correlate the clinical, radiographic, and pathologic features in order to better understand its pathogenesis and behavior and facilitate proper therapy.

Design.—Adult autopsies performed at a tertiary care center from 1978 to 2004 were reviewed to identify cases of DPO. Clinical, radiographic, and pathologic findings, including ultrastructural studies in select cases, were analyzed and correlated.

Results.—Eight cases of DPO were identified from 1393 adult autopsies. None of the cases was diagnosed antemortem. The prevalence of DPO was 0.5%, and the incidence was 0.28 cases per year. Most patients had a history of chronic lung disease, and all were 65 years of age or older.

Conclusions.—Dendriform pulmonary ossification is an uncommon and unusual entity seen incidentally at autopsy and associated with chronic lung disease. It is well demonstrated in postmortem examination, confirmed by microscopy and ultrastructural study, but rarely diagnosed and virtually never considered clinically. Clinical diagnoses include bronchiectasis and interstitial pneumonitis based on radiographic evidence. With its associated radiographic/pathologic findings, DPO should be considered in the differential diagnosis of chronic lung disease.
Recurrence of Nodal Diffuse Large B-Cell Lymphoma as Intravascular Large B-Cell Lymphoma: Is an Intravascular Component at Initial Diagnosis Predictive?
Authors: Zhao Xian-Feng , Sands Amy M. , Ostrow Peter T. , Halbiger Regina , Conway James T. , Bagg Adam
Published: February 2021

We report a case of a 59-year-old man who first presented with a nodal diffuse large B-cell lymphoma that later relapsed as an intravascular large B-cell lymphoma. In the initial biopsy specimen, a few intranodal small vessels that contained large lymphoma cells were noted. After 8 months of multiagent chemotherapy, clinical remission was attained. Two years after the initial diagnosis of nodal diffuse large B-cell lymphoma, the patient presented with a rapid onset of multiorgan failure, which at autopsy was shown to be due to intravascular large B-cell lymphoma. Molecular genetic studies showed that these 2 lymphomas had immunoglobulin heavy-chain gene rearrangements that were of identical size, suggesting that they were derived from the same clone. To our knowledge, this is the first report of a nodal large B-cell lymphoma that relapsed as an intravascular large B-cell lymphoma. Although this report is of only a single case, the presence of a relatively inconspicuous intravascular component in an otherwise typical nodal large B-cell lymphoma may be predictive and could affect clinical decisions regarding diagnosis, monitoring, and prognosis of such lymphomas.
Cardiac Aspergillosis in Patients With Acquired Immunodeficiency Syndrome: A Case Report and Review of the Literature
Authors: Xie Linjun , Gebre Wondwossen , Szabo Katarina , Lin Jen H.
Published: February 2021

Cardiac aspergillosis is uncommon in patients with acquired immunodeficiency syndrome (AIDS) in the absence of open heart surgery. We report a unique case of a 62-year-old man with AIDS who developed Aspergillus pancarditis with Aspergillus vegetations on mitral valve without evidence of pulmonary aspergillosis. There was extensive embolization to the brain and multiple foci of Aspergillus infection in kidneys and adrenal glands. There are only 10 documented cases of cardiac aspergillosis in the literature (1966–2003) in severely immunocompromised AIDS patients with CD4 T-lymphocyte counts ranging from 10 to 121 cells/μL. The cardiac aspergillosis could result from invasive pulmonary aspergillosis, either by hematogenous dissemination or by direct invasion, and skin Aspergillus infection can be carried through the bloodstream to the right heart in intravenous drug abusers. Most of the reported cases of cardiac aspergillosis were diagnosed at autopsy. Mortality among AIDS patients with cardiac aspergillosis is 100%, despite appropriate therapy.
Detection of Microinvasion in Vulvar and Cervical Intraepithelial Neoplasia Using Double Immunostaining for Cytokeratin and Basement Membrane Components
Authors: Rush Demaretta , Hyjek Elizabeth , Baergen Rebecca N. , Ellenson Lora H. , Pirog Edyta C.
Published: February 2021

Context.—Identification of early invasion in vulvar intraepithelial neoplasia 3 (VIN 3) and cervical intraepithelial neoplasia 3 (CIN 3) may be difficult with the use of routine hematoxylin-eosin staining. Presence of obscuring inflammation and tangential tissue sectioning are the most common diagnostic pitfalls.

Objective.—To examine the utility of double immunostaining for cytokeratin–collagen IV or cytokeratin-laminin in the detection of early invasion in VIN 3 and CIN 3.

Design.—The study group consisted of 10 cases of “VIN 3, suspicious for invasion” and 10 cases of “CIN 3, suspicious for invasion.” The negative control group consisted of VIN 3 (n = 15) and CIN 3 (n = 10). The positive control group consisted of cases of invasive vulvar carcinoma (n = 11) and invasive cervical carcinoma (n = 25). All cases were double immunostained for cytokeratin and collagen IV and, in a separate reaction, for cytokeratin and laminin. The continuity of the basement membrane and the presence of stromal invasion were assessed in the stained sections.

Results.—The staining for collagen IV and laminin yielded identical results. A well-defined, continuous basement membrane was visualized in all cases of VIN 3 and CIN 3. A discontinuous or absent basement membrane was observed around the malignant cells on the invasive tumor front in all cases of vulvar and cervical carcinoma. In 2 of 10 cases of VIN 3, suspicious for invasion and in 4 of 10 cases of CIN 3, suspicious for invasion definitive foci of microinvasion were identified with the use of double immunostaining. A well-defined, continuous basement membrane was present in the remaining cases “suspicious for invasion.”

Conclusion.—Double immunostaining for cytokeratin– collagen IV or cytokeratin-laminin is useful for evaluation of early invasion in equivocal cases of VIN 3 and CIN 3.
Immunohistochemical Expression of β-Catenin in Solitary Fibrous Tumors
Authors: Rakheja Dinesh , Molberg Kyle H. , Roberts Cory A. , Jaiswal Vilkesh R.
Published: February 2021

Context.—Immunohistochemical staining for β-catenin may be used as an indicator of the integrity of the Wnt signaling and β-catenin degradation pathways. Among mesenchymal tumors, aberrant nuclear localization of β-catenin is seen in desmoid-type fibromatoses but has not been described for solitary fibrous tumors that may mimic the former lesions, especially in small biopsy samples.

Objective.—To study the immunohistochemical expression of β-catenin in solitary fibrous tumors.

Design.—We performed immunohistochemical staining for β-catenin in 12 solitary fibrous tumors, one of which showed histologic features of malignancy.

Results.—All the tumors showed strong and diffuse reactivity for β-catenin. Four tumors (33%) showed nuclear staining for β-catenin, whereas the remaining tumors showed either a membranous or mixed membranous and cytoplasmic pattern of staining. The only histologically malignant tumor of the group showed a mixed membranous and cytoplasmic pattern of staining for β-catenin.

Conclusions.—Immunohistochemical staining for β-catenin in solitary fibrous tumors does not show a consistent pattern, which may be due to differences in tumorigenesis. Larger studies with clinical follow-up are required for estimating the impact of the variable staining pattern on clinical behavior of these tumors.
Sudden Death of a Patient With Pulmonary Langerhans Cell Histiocytosis
Authors: Nakhla Hassan , Jumbelic Mary I.
Published: February 2021

We report a case of sudden death due to bilateral pneumothorax in a previously healthy 16-year-old adolescent white girl. She presented with sudden onset of shortness of breath followed by loss of consciousness. Postmortem chest radiograph showed bilateral pneumothoraces. Autopsy confirmed the bilateral pneumothorax and additionally showed emphysematous changes and bullae throughout the lung tissue. Microscopic sections of the lungs showed Langerhans cell histiocytosis. To the best of our knowledge, this is the first reported case of fatal presentation of pulmonary Langerhans cell histiocytosis.
Malignant Glomus Tumor of the Urinary Bladder
Authors: Shim Hyo Sub , Choi Young Deuk , Cho Nam Hoon
Published: February 2021

We present a case of a malignant glomus tumor arising in the urinary bladder of a 57-year-old woman with metastatic pulmonary nodules who died 2 months later. Pathologically and clinically confirmed malignant glomus tumors are exceedingly rare, especially those that arise in the visceral organs. The present case retained its architectural similarity to a benign glomus tumor and consisted of sheets of highly malignant round cells showing cytoplasmic positivity for smooth muscle actin. On reticulin histochemical staining, we found that reticulum fibrils surrounded individual tumor cells, suggesting cellular investment by basement membrane. We discuss the concept of malignant glomus tumors and emphasize the criteria that distinguish them from other malignant tumors.
Cytomegalovirus Infection Masquerading as Carcinoma in a Lung Transplant Patient
Authors: Allen Timothy Craig , Bag Remzi , Zander Dani S. , Cagle Philip T.
Published: February 2021

In lung transplant patients, most infections produce radiographically diffuse or lobar infiltrates. Solitary nodules suggesting neoplasm may arise in lung transplant patients with lung infections. We describe a 45-year-old woman who underwent bilateral lung transplantation to treat bilateral bronchiectasis and lung fibrosis resulting from Hodgkin disease. Five months later, a solitary mass was identified on chest radiograph in the left upper lobe and left superior mediastinum. Low-power examination of wedge biopsies of the mass showed a florid proliferation of cells with clear to bubbly to eosinophilic cytoplasm and moderate nuclear atypia, proliferating fibroblasts, and necrosis, suggesting a clear cell carcinoma (possibly metastatic renal cell carcinoma). Intranuclear inclusions compatible with cytomegalovirus were identified on high-power examination and confirmed by immunohistochemistry. In lung transplant patients, a cytomegalovirus infection may mimic malignancy both radiographically and on initial histopathologic examination.
Clear Cell Hidradenoma: A Mimic of Metastatic Clear Cell Tumors
Authors: Volmar Keith E. , Cummings Thomas J. , Wang Wei Hua , Creager Andrew J. , Tyler Douglas S. , Xie H. Bill
Published: February 2021

Clear cell hidradenoma is a benign skin appendage tumor that may mimic conventional-type renal cell carcinoma. Histologically, clear cell hidradenoma contains small ductular lumens, focal apocrine and squamoid change, and a less prominent vascular pattern than renal cell carcinoma. Furthermore, immunohistochemical studies can aid in distinguishing the 2 tumors. Knowing the cytologic features of primary skin adnexal neoplasms helps distinguish them from cutaneous metastases, which are more commonly referred for fine-needle aspiration biopsy evaluation. Detailed clinical history, physical findings, and ancillary studies are essential for correct diagnosis and categorization of these tumors. We report the rare case of a patient with renal cell carcinoma who underwent excision of an axillary clear cell hidradenoma, which was clinically suggestive of cutaneous metastatic disease.
Adrenocortical Carcinoma With Concomitant Myelolipoma in a Patient With Hyperaldosteronism
Authors: Sun Xichun , Ayala Alberto , Castro Claudia Y.
Published: February 2021

We present a case of aldosterone-secreting adrenocortical carcinoma with concomitant myelolipoma. To the best of our knowledge, this is the first such reported case. The patient was a 43-year-old man with severe hypertension. Clinical workup revealed an increased serum aldosterone level, hypokalemia, and metabolic alkalosis, and a left adrenal mass was found on computed tomography. The patient underwent a unilateral adrenalectomy, which led to improvement in blood pressure, the serum potassium level, and aldosterone concentration. The tumor weighed 70 g and measured 5.0 cm. On microscopic examination, we found necrosis, focal cytologic atypia, diffuse eosinophilic cells comprising more than 75% of the tumor, 5 to 7 mitotic figures per 50 high-power fields, rare atypical mitosis, and venous invasion. At the periphery of the tumor but within the capsule, microscopic areas of myelolipoma were seen. Ki-67 staining was positive in 20% of the tumor cells. Although rare, aldosterone-secreting carcinoma associated with myelolipoma should be included in the differential diagnosis of adrenal gland masses.
Intramuscular Juvenile Xanthogranuloma in an Adult
Authors: Kuo Fang-Ying , Eng Hock-Liew , Chen Shih-Hao , Huang Hsuan-Ying
Published: February 2021

Juvenile xanthogranuloma (JXG) is a self-limited cutaneous lesion that most often occurs in infancy. Approximately 10% to 30% of JXGs occur in adult patients, where most cases present as cutaneous papulonodular lesions, with only rare cases involving extracutaneous sites. Intramuscular JXG is extremely rare and has received little attention. On review of the literature, all of the 6 previously reported intramuscular JXGs were noted in the pediatric population. The authors hereby describe a case of adult intramuscular JXG that occurred in a woman who initially had a dermal JXG in the nasal skin at the age of 48 years and then developed a slow-growing painless intramuscular JXG in the right forearm 4 years later. Both the dermal and intramuscular lesions revealed similar histologic features and consisted of diffuse infiltrates of histiocytes with eosinophilic and foamy cytoplasm, lymphocytes, eosinophils, and Touton giant cells in varying proportions. However, central fibrosis and a focal storiform arrangement of spindled fibroblast-like cells in the intramuscular lesion resulted in a histologic pattern reminiscent of a fibrous histiocytoma. Immunohistochemically, the intramuscular JXG was positive for CD68, factor XIIIa, CD31, and vimentin. This case underscores the fact that intramuscular JXG can also involve adult patients and its morphologic variation is more likely to be time dependent rather than site specific or age related.
Fulminant Multisystem Non–Langerhans Cell Histiocytic Proliferation With Hemophagocytosis
Authors: Rao R. Nagarjun , Chang Chung-che , Uysal Nevin , Presberg Kenneth , Shidham Vinod B. , Tomashefski Joseph F.
Published: February 2021

Hemophagocytosis (HP), a feature seen in malignant histiocytosis and infection- and lymphoma-associated disorders, has not been previously emphasized in Erdheim-Chester disease (ECD). Generally, ECD is recognized as a rare, systemic, non–Langerhans cell histiocytosis with a variable clinical course. Herein, we describe a unique case of multisystem non–Langerhans cell histiocytic proliferation with a fulminant clinical course (death occurred within 3 months of presentation) that showed prominent HP and extensive involvement of multiple organs, including the lungs, resulting in respiratory failure. Hemophagocytosis led to severe anemia that required transfusion and thrombocytopenia. Antemortem lung and bone marrow biopsy specimens revealed involvement by a histiocytic infiltrate with features highly suggestive of ECD and HP. Furthermore, the autopsy documented the presence of HP and the histiocytic infiltrate in multiple other organs. This case is best categorized as a variant form of ECD. Recognizing this variant has the following important implications: (1) HP may be a marker for fulminant clinical course in ECD, (2) the presence of HP does not exclude a diagnosis of ECD, and (3) ECD should be considered in the differential diagnosis of HP.
Rhabdoid Tumor of the Thyroid Gland: A Variant of Anaplastic Carcinoma
Authors: Lai Maria Letizia , Faa Gavino , Serra Stefano , Senes Giancarlo , Daniele Giovanni M. , Boi Francesco , Mariotti Stefano , Beauchemin Michel , Asa Sylvia L.
Published: February 2021

Rhabdoid tumor of the thyroid gland is a very rare neoplasm, characterized by significant metastatic potential. All of the 6 cases reported in the recent literature had poor outcomes. We report an additional case involving, to our knowledge, the oldest patient reported so far. A 67-year-old woman had a nodular goiter for all of her adult life and presented with a rapidly growing mass in the right lobe. Histologic examination showed a highly cellular neoplasm with a solid infiltrative growth pattern. Extracapsular invasion was evident. Rhabdoid cells were large, with abundant cytoplasm, eosinophilic inclusions, and eccentric nuclei containing distinct nucleoli. Immunohistochemistry identified vimentin, sarcomeric actin, myoglobin, and cytokeratin expression in the tumor cells; they were negative for desmin, thyroglobulin, and calcitonin. Scattered follicles with nuclear features of papillary thyroid carcinoma were detected; these cells were immunoreactive for thyroglobulin and TTF-1. Reverse transcriptase polymerase chain reaction using specific primers for RET/PTC1 and RET/PTC3 fusion genes identified a RET/PTC3 gene rearrangement in the rhabdoid tumor. Despite radiotherapy, the neoplasm rapidly progressed, with massive local and mediastinal metastasis leading to death 5 months after presentation. The hypothesis that rhabdoid tumor is a variant of anaplastic thyroid carcinoma is supported by the identification of a RET/PTC gene rearrangement, a feature of carcinomas of follicular cell derivation.
Renal Failure and Nephrocalcinosis Associated With Oral Sodium Phosphate Bowel Cleansing: Clinical Patterns and Renal Biopsy Findings
Authors: Gonlusen Gulfiliz , Akgun Hulya , Ertan Atilla , Olivero Juan , Truong Luan D.
Published: February 2021

Acute renal failure (ARF) is rarely reported after bowel preparation with sodium phosphate. We report a patient with mild Crohn disease (in remission), without history of renal disease, and with normal baseline renal function, who developed ARF 14 days after bowel preparation for colonoscopy with oral sodium phosphate. A renal biopsy showed multifocal calcium phosphate deposition in the renal tubules against a background of diffuse chronic tubulointerstitial injury. Review of the literature suggested 2 distinct patterns of ARF in the context of sodium phosphate bowel cleansing. One pattern is characterized by ARF, which develops a few hours or days after sodium phosphate administration, as a component of a systemic syndrome associated with severe hyperphosphatemia and hypocalcemia. Correction of these electrolyte abnormalities was frequently associated with rapid recovery of renal function. The cause of ARF in this context was not clear because the favorable outcome negated the need for renal biopsy. In the second pattern, exemplified by the current patient, ARF was identified incidentally. These patients did not have any features of an acute syndrome immediately after sodium phosphate administration and presented much later (usually weeks) with mild, nonspecific symptoms. At the time of presentation, the serum calcium and phosphate levels were normal. The renal biopsies in each of these patients showed nephrocalcinosis as the possible cause of ARF. The renal failure improved at least partially in most of these patients, but persisted in rare cases.
Interobserver Agreement in Hepatitis C Grading and Staging and in the Banff Grading Schema for Acute Cellular Rejection: The “Hepatitis C 3” Multi-Institutional Trial Experience
Authors: Netto George J. , Watkins David L. , Williams James W. , Colby Thomas V. , dePetris Giovanni , Sharkey Francis E. , Corless Christopher L. , Lewin David , Petrovic Lydia , Sharma Shobha , Kanel Gary , Theise Neil , West A. Brian , Koehler Alison , Jhala Nirag C. , Lefkowitch Jay , Lezzoni Julia , Jennings Linda W. , Tillery G. Weldon , Klintmalm Goran B.
Published: February 2021

Context.—Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials.

Objective.—To evaluate interobserver agreement in assessing chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17 hepatopathologists involved in the “Hepatitis C 3” trial.

Design.—The trial is a randomized multicenter (17 institutions) study involving 312 patients undergoing transplantation for HCV. Patients are randomized to 3 treatment arms. For final data analysis, all biopsy specimens are reviewed by a central pathologist (G.J.N.). Recurrence of HCV is evaluated according to the Batts and Ludwig schema. The 1997 Banff schema is used to evaluate ACR. To assess interobserver agreement, hematoxylin-eosin–stained sections from 11 liver biopsy specimens (6 HCV and 5 ACR) were sent by the central pathologist to 16 local pathologists from 13 institutions. Statistical analysis was performed on raw ACR/HCV data as well as data grouped according to clinically significant primary endpoint cutoffs.

Results.—Statistically significant agreement was found among all participating pathologists (P < .001). On κ analysis, the degree of agreement was rated “moderate” for HCV grade and stage and ACR global grading (κ = 0.30, 0.33, and 0.37, respectively). Interobserver agreement was weaker for rejection activity index scoring of ACR (κ = 0.15). A stronger degree of agreement was found when scores were grouped based on endpoint cutoffs (κ = 0.76 “almost perfect” for HCV and 0.62 “substantial” for ACR).

Conclusions.—An overall statistically significant interobserver agreement was found among 17 pathologists using the 1997 Banff schema and the Batts and Ludwig schema.
Histopathologic Findings of Malformations of Cortical Development in an Epilepsy Surgery Cohort
Authors: Morris E. Brannon , Parisi Joseph E. , Buchhalter Jeffrey R.
Published: February 2021

Context.—Malformations of cortical development (MCDs) are an important cause of pharmacoresistent epilepsy and are frequently diagnosed in surgical pathology. The lack of uniform tissue processing and standard histopathologic nomenclature to describe MCDs has resulted in diagnostic ambiguity.

Objective.—To describe the immunohistochemical findings of MCDs from a relatively large surgical epilepsy cohort and incorporate terminology that more adequately reflects the histopathologic findings into a contemporary classification of MCD.

Design.—Utilizing the Mayo Clinic Rochester Surgical Pathology Database and patient records, 53 patients with previous intractable epilepsy and a known malformation of cortical development were identified. All of the cohort's paraffin embedded surgical specimens were resectioned and stained with hematoxylin-eosin, Luxol fast blue/cresyl violet, neurofilament protein, and glial fibrillary acidic protein. Each specimen was reviewed histologically and categorized according to a proposed focal MCD classification scheme that substitutes cytoarchitectural dysmorphism for cortical dysplasia and architectural disorganization for microdysgenesis.

Results.—An MCD was recognized in 49 patients and grouped into 1 of the following 4 categories: (1) cytoarchitectural dysmorphism with balloon cells (n = 19), (2) cytoarchitectural dysmorphism without balloon cells (n = 12), (3) architectural disorganization (n = 8), or (4) polymicrogyria (n = 9).

Conclusions.—The histopathologic features of focal MCD in a large epilepsy surgical cohort by using practical immunohistochemistry and a contemporary MCD classification scheme are described. It is proposed that the term focal cortical dysplasia be renamed as focal malformations of cortical development.
Allelic Loss of 3 Different Tumor Suppressor Gene Loci in Benign and Malignant Endothelial Tumors of the Head and Neck
Authors: Domfeh Akosua B. , Fichera Michelle , Hunt Jennifer L.
Published: February 2021

Context.—Angiosarcomas are rare malignancies that commonly arise in the head and neck. No definitive precursor lesion or etiological link between hemangiomas and angiosarcoma has been postulated. Evidence at the cell culture level suggests that loss of heterozygosity of 13q might be involved in tumorigenesis of endothelial cells. Although overexpression of p53 and WT-1 has been found in angiosarcoma, little is known about the molecular changes involved.

Objective.—This study compared the molecular profile of angiosarcoma with that in some benign vascular lesions.

Design.—Specimens from 6 cases of angiosarcoma, 5 of hemangioma, and 5 of granulation tissue were microdissected. DNA extraction and polymerase chain reaction amplification for 11 microsatellite markers on chromosomes 11p13, 13q14, and 17p13 (WT-1, RB, p53) were performed. Loss of heterozygosity of amplification products was assessed by capillary electrophoresis. Allelic loss and fractional allelic loss were calculated.

Results.—The mean fractional allelic loss was 43% for angiosarcomas and 29% for hemangiomas. Eighty-three percent of angiosarcomas had allelic loss at 17p13, 66% at 13q14, and 50% at 11p13. Allelic loss was seen in 60% of hemangiomas at 13q14 and 17p13, but only in 20% at 11p13. Two cases of hemangioma and all the granulation tissue cases had no allelic losses.

Conclusions.—In our study, 11p13, 13q14, and 17p13 allelic losses were present in both hemangiomas and angiosarcomas. This supports the cell culture–based theories that tumorigenesis in endothelial cells likely involves these chromosomes and provides some insight into the potential pathogenesis of angiosarcomas and benign hemangiomas.
Mesenchymal Hamartoma of the Liver With an Interstitial Deletion Involving Chromosome Band 19q13.4: A Theory as to Pathogenesis?
Authors: Talmon Geoffrey A. , Cohen Samuel M.
Published: February 2021

Mesenchymal hamartoma of the liver is the third most common liver tumor of infancy. The lesion is primarily mesenchymal in origin, believed to arise from a developmental abnormality in the formation of ductal plates during late embryogenesis. Several studies have revealed a recurrent translocation in mesenchymal hamartomas, all involving a breakpoint at chromosome band 19q13.4. We present a case with a deletion involving this locus. A 10-month-old girl presented with an asymptomatic abdominal mass. The 21.0-cm tumor arose from the surface of the liver. The cut surfaces displayed multiple cysts with intervening loose fibrous tissue. Microscopically, the tumor was mostly composed of edematous connective tissue with intervening cysts, islands of hepatocytes, and haphazard branching bile ducts. Cytogenetic analysis revealed an interstitial deletion on the long arm of chromosome 19(q13.1q13.4). The patient was discharged on postoperative day 4 without complications. The cytogenetic findings support the involvement of an alteration of a gene at chromosome band 19q13.4 in the pathogenesis of mesenchymal hamartoma of the liver.
Medical Examiners, Coroners, and Public Health: A Review and Update
Authors: Hanzlick Randy
Published: February 2021

Context.—Traditionally, the emphasis of work done by medical examiners, coroners, and the death investigation community has been viewed as serving the criminal justice system. During the last several decades, however, an important role for these 3 groups has emerged within public health.

Objective.—To provide important background information on death investigation systems, the evolution and framework of public health entities that rely on information gathered by medical examiners and coroners, and the role of medical examiners and coroners in epidemiologic research, surveillance, and existing public health programs and activities.

Data Sources.—Previous articles on epidemiologic aspects of forensic pathology and the role of medical examiners and coroners in epidemiologic research and surveillance; a review of the Web sites of public health and safety agencies, organizations, and programs that rely on medical examiner and coroner data collected during medicolegal investigations; and a review of recent public health reports and other publications of relevance to medical examiner and coroner activities.

Conclusions.—The role of medical examiners and coroners has evolved from a criminal justice service focus to a broader involvement that now significantly benefits the public safety, medical, and public health communities. It is foreseeable that the public health role of medical examiners and coroners may continue to grow and that, perhaps in the not-too-distant future, public health impact will surpass criminal justice as the major focus of medicolegal death investigation in the United States.