bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic Mucinous Cystic Neoplasm of the Main Pancreatic Duct
Authors: Masia Ricard , Mino-Kenudson Mari , Warshaw Andrew L , Pitman Martha B , Misdraji Joseph
Published: February 2021

Mucinous cystic neoplasm and intraductal papillary mucinous neoplasm are 2 types of cystic pancreatic mucinous tumors, each with its own distinct clinicopathologic features and pathogenetic mechanisms. We report here an unusual pancreatic mucinous neoplasm with features of both a mucinous cystic neoplasm and an intraductal papillary mucinous neoplasm in a 40-year-old woman who underwent total pancreatectomy. The endoscopic retrograde cholangiopancreatogram and gross examination demonstrated a mucin-producing intraductal neoplasm involving the length of the main pancreatic duct, typical of main duct intraductal papillary mucinous neoplasm, but histology of the main duct showed involvement by a biphasic tumor composed of columnar epithelium overlying ovarian-type stroma, characteristic of a mucinous cystic neoplasm. Immunohistochemistry confirmed that the stromal cells expressed estrogen and progesterone receptors, inhibin, and calretinin. Pancreatic mucinous cystic neoplasm involving the entire main pancreatic duct has not, to our knowledge, been previously reported.
Immunohistochemical Characterization of p57Kip2 Expression in Tetraploid Hydropic Placentas
Authors: Fukunaga Masaharu
Published: February 2021

Context.—Because there are differences in the origin, morphology, and natural history of hydropic placental villous issues, it is important to identify and document rare specimens that deviate from the diploid complete hydatidiform mole (CM), triploid partial hydatidiform mole (PM), or diploid hydropic abortion (HA). Tetraploid hydropic placentas have rarely been studied.

Objectives.—To evaluate the frequency of p57Kip2 protein (p57) expression in tetraploid hydropic placentas and to determine its clinicopathologic significance.

Design.—Forty hydropic DNA tetraploid placental specimens were evaluated by immunohistochemistry of formalin-fixed tissues, using a monoclonal antibody against p57, a putative paternally imprinted inhibitor gene. DNA ploidy in all cases was analyzed by flow cytometry.

Results.—Thirty cases were histologically diagnosed as CMs, 10 were HAs, and none were PMs. In all HAs, nuclear p57 was strongly expressed in cytotrophoblasts, intermediate trophoblasts, and villous stromal cells. In contrast, in CMs, p57 expression in cytotrophoblasts and villous stromal cells was either absent (26 cases) or very low (4 cases). Assuming that the degree of molar change roughly correlates with the proportion of paternal chromosomes present, all chromosomes might be paternally derived in all tetraploid CMs and the 10 HAs, including 2 that were karyotyped as 92,XXYY or 90,XXYY,−13,−14, which were presumably due to 2 sets of chromosomes each from paternal and maternal origin.

Conclusions.—Expression of p57 is aberrant in tetraploid CMs. This finding is in line with the hypothesis that the loss of p57 is involved in the abnormal development of androgenetic CMs. For the evaluation of a patient with trophoblastic disease, p57 immunostaining is an ancillary diagnostic method that may be used in concert with flow cytometry.
Paneth Cell Carcinoma of the Ampulla of Vater
Authors: Mora Jorge I. , Barroeta Julieta E. , Bernstein David A. , Lechago Juan
Published: February 2021

We describe a Paneth cell carcinoma arising within the ampulla of Vater in a 64-year-old man. The phenotype of virtually all neoplastic cells was consistent with that of Paneth cells, based on routine morphology and their strong positive immunostaining for lysozyme. Additional widespread positive immunostaining for carcinoembryonic antigen and CA 19.9 supports a totipotential cell as the origin of such neoplastic cells. This case, therefore, represents a true Paneth cell carcinoma, as opposed to inclusion of occasional neoplastic Paneth cells into a poorly differentiated adenocarcinoma. This pattern of differentiation is rare, and predictions regarding its ultimate biological behavior and malignant potential must be guarded.
Challenge in Diagnosis of CD56+ Lymphoproliferative Disorders: Two Cases of CD56+CD33+ Lymphoma/Leukemia
Authors: Yang Xu , Wasserman Patricia G. , Bhargava Archana , Iqbal Uzma , Ragnauth Shrutikant , Fuchs Alexander
Published: February 2021

Two cases of CD56+CD33+ leukemia/lymphoma are reported. The patient in case 1 presented with skin rash, diffuse lymphadenopathy, and hepatosplenomegaly. Blasts with monocytoid and lymphoid features were present in the peripheral blood. The tumor cells expressed HLA-DR, CD4, CD33, CD38, and CD56. Cytogenetic analysis revealed del(2)(p13),del(9)(q22),add(6)(q25),add(12)(p12),−13,−18, and −20. The clinicopathologic features were similar to those of blastic natural killer cell leukemia/lymphoma or type 2 dentritic cell leukemia. The patient in case 2 presented with generalized weakness and skin erythema not responding to antibiotics. Circulating blasts with monocytoid features were seen in the peripheral blood. The tumor cells expressed CD7, CD13, CD33, CD38, and CD56, and cytogenetic analysis revealed −5,add(7)(p22),−8, del(10)(p11.2),−12,der(13; 14)(p10;p10),+14,−16,−18,−19, and del(20)(q13.1). The clinicopathologic features were consistent with a myeloid/ natural killer cell precursor acute leukemia. Both disorders are aggressive hematopoietic malignancies that have similar clinical presentation and morphology but differ in immunophenotype and cytogenetic features.
Posttransplant Primary Cutaneous Ki-1 (CD30)+/CD56+ Anaplastic Large Cell Lymphoma
Authors: Kim Hee Kyung , Jin So-Young , Lee Nam Su , Won Jong Ho , Park Hee Sook , Yang Woo Ick
Published: February 2021

An anaplastic large cell lymphoma that was negative for Epstein-Barr virus and positive for Ki-1 (CD30) presented as a polypoid scalp mass in a 56-year-old man 16 years after renal transplantation. The lymphoma was of the CD4+ cytotoxic T-cell lineage, and the tumor cells also expressed CD56. Despite reduction in the dose of immunosuppression and localized radiotherapy, the tumor had rapidly progressed to involve the soft tissue of the right hand. Systemic chemotherapy induced complete regression of the soft tissue lesion. This case illustrates that posttransplant primary cutaneous CD30+ anaplastic large cell lymphomas may assume an aggressive clinical course but can still be controlled by systemic chemotherapy.
Measuring the Significance of Field Validation in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology: How Good Are the Experts?
Authors: Renshaw Andrew A. , Wang Edward , Mody Dina R. , Wilbur David C. , Davey Diane D. , Colgan Terence J.
Published: February 2021

Context.—Expert opinion is often used as a gold standard for gynecologic cytology in the evaluation of new technologies, in the legal setting, and in the validation of cases for use in educational programs and proficiency testing. However, the reliability of expert opinion alone in selecting slides of a specific cytodiagnosis that can be reproducibly and reliably identified by subsequent reviewers has not been determined.

Objective.—To assess the ability of expert opinion to select slides that are validated in subsequent reviews.

Design.—In the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, each case in every cytodiagnostic category is accepted for circulation only after review by 3 expert cytopathologists. The percentage of these cases that could not be reliably and reproducibly identified by program participants for each cytodiagnostic category (“failed field validation”) was determined during the duration of the program from 1989 to 2004.

Results.—More than 10 000 conventional smears and ThinPrep cases were selected by the expert panel for circulation. Of these selected slides, 19% of conventional smears and 15% of ThinPrep specimens failed field validation. Compared with the overall slide performance, significantly higher percentages (P < .001) of conventional smears with reference diagnoses of unsatisfactory (51.7%), repair (58%), or low-grade intraepithelial lesion (31.8%) and of ThinPrep specimens with reference diagnoses of unsatisfactory (54.5%) and repair (76.9%) failed field validation. In contrast, significantly lower percentages of conventional smears with reference diagnoses of squamous cell carcinoma (4.5%), high-grade squamous intraepithelial lesion (9%), Trichomonas vaginalis infection (11.7%), or herpes (9.9%) and of ThinPrep specimens with reference diagnoses of adenocarcinoma (5.1%), herpes (2.1%), and fungal organism consistent with Candida (8.4%) failed field validation (P < .001 for all).

Conclusions.—Between 15% and 19% of gynecologic cytologic cases that have been selected by expert cytopathologists as good examples of cytodiagnostic abnormalities fail field validation. The proportion of cases failing field validation varies with cytodiagnostic category, but it occurs in all cytodiagnostic entities.
Glioblastomas in the Older Old
Authors: Kleinschmidt-DeMasters B. K. , Lillehei K. O. , Varella-Garcia M.
Published: February 2021

Context.—Recent studies have identified fundamental biological differences in the effects of epidermal growth factor receptor (EGFR) amplification on survival in older versus younger patients with glioblastoma multiforme (GBM). Cell cycle labeling indices have also been found to be inordinately high in older GBM patients and may contribute to the known adverse prognosis in this cohort. However, testing has not been conducted on significant numbers of patients of very advanced age, in whom these features might be expected to emerge as even more significant factors.

Objective.—To assess EGFR amplification status and MIB-1 indices in patients with GBM who are older than 75 years.

Design.—We identified 20 patients (female-male ratio, 11:9; 11 aged 75–79 years and 9 aged 80–87 years) and studied tumor tissue samples with immunohistochemistry for cell cycle labeling index and by fluorescence in situ hybridization for EGFR amplification. Survival data were obtained from the Colorado Tumor Registry.

Results.—Mean MIB-1 index was high (24.8%), but individual indices did not correlate with survival. EGFR amplification was detected in 25% of cases, with gain of chromosome 7 in all but one of the remaining patients. Ninety-five percent of patients manifested EGFR amplification and/or polysomy of chromosome 7. Heterogeneity was found within a given tumor, with 10% to 60% of cells showing gain of chromosome 7. Overall patient survival was poor (mean, 4.6 months), but was significantly longer in those with EGFR gene amplification (mean, 8.3 months; median, 10.5 months) versus those without (mean, 3.2 months; median, 2.0 months) (P = .04).

Conclusion.—The presence of EGFR amplification is a significant predictor of survival time in older old patients.
Hematologic Malignancies With Primary Retroperitoneal Presentation: Clinicopathologic Study of 32 Cases
Authors: Chen Lei Lei , Kuriakose Philip , Hawley Robert C. , Janakiraman Nalini , Maeda Koichi
Published: February 2021

Context.—The retroperitoneum is an uncommon location for primary lymphomatous involvement. Initial presentation of disease in this site (primary retroperitoneal lymphoma) is considered to be rare. Because of the uncommon anatomic location, the diagnosis and subsequent management of these patients tend to be difficult for both pathologists and clinicians.

Objective.—This report describes our experience during a period of 6 years 4 months with patients with hematologic malignancies primarily presenting in the retroperitoneum.

Design.—A retrospective search of our medical records generated 32 patients who presented initially with abdominal pain or discomfort as their predominant symptom and who were found by imaging studies to have retroperitoneal mass or masses. All the histopathology slides were reviewed and classified based on the World Health Organization classification.

Results.—There were 13 male and 19 female patients. Tumor types included diffuse large B-cell lymphoma (n = 12); grade 1 follicular lymphoma (n = 4); grade 3 follicular lymphoma (n = 1); B chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 2); multiple myeloma (n = 1); mixed-cellularity Hodgkin lymphoma (n = 1); nodular sclerosis Hodgkin lymphoma (n = 1); aggressive B-cell lymphoma (n = 4); low-grade B-cell lymphoma (n = 4); lymphoblastic lymphoma, null cell type (n = 1); and precursor B-lymphoblastic lymphoma/leukemia (n = 1). More than half of the cases (17/32) were diagnosed on needle biopsy with immunophenotyping.

Conclusions.—Although open lymph node biopsy is a preferred method for diagnosis, needle biopsy plays a significant role in this setting, and, coupled with other information such as flow cytometry and immunohistochemistry, it is considered a practical and reliable method.
Pulmonary Adenocarcinomas Associated With Rheumatoid Nodules: A Case Report and Review of the Literature
Authors: Baruch Amy C. , Steinbronn Karen , Sobonya Richard
Published: February 2021

Necrobiotic lung nodules and primary lung carcinoma both occur with some frequency in patients with rheumatoid arthritis; however, few reports exist of a primary lung carcinoma occurring within a rheumatoid nodule. We report a case of a 62-year-old woman with multiple pulmonary nodules discovered incidentally by computed tomography. Although 2 of the lesions were composed solely of necrotizing granulomas, 2 additional lesions contained malignant glands at the periphery of necrobiotic nodules. Immunohistochemical staining supported the diagnosis of both tumors as primary lung carcinomas. Our literature search revealed only 2 other reported cases of adenocarcinoma occurring in association with a rheumatoid nodule; these cases, as well as the association between rheumatoid disease and malignancy, are briefly reviewed.
Myocarditis Temporally Related to the Use of Gefitinib (Iressa)
Authors: Truell Jeff S. , Fishbein Michael C. , Figlin Robert
Published: February 2021

Gefitinib is a new drug that was approved by the US Food and Drug Administration in May 2003 for non–small cell cancer of the lung refractory to first- and second-line therapy. It is regarded as a rather safe drug with common adverse effects that include nausea, vomiting, diarrhea, rash, acne, and dry skin. However, it was reported in Japan to be associated with interstitial pneumonitis (2%–3% of subjects), presumably as a manifestation of a hypersensitivity reaction. The Food and Drug Administration studied this in US patients and found only a 0.3% occurrence and a slightly less than 0.1% mortality due to interstitial pneumonitis. To our knowledge, there has not been an association with fulminant myocarditis or acute myocarditis. We report the case of a 71-year-old man who died as a result of fulminant myocarditis 1 week after starting to take this new class of agent, gefitinib. On the basis of his medical history and our findings, we feel it necessary to consider hypersensitivity myocarditis related to gefitinib the probable cause of death.
Fine-Needle Aspiration Diagnosis of Angiosarcoma of the Spleen: A Case Report and Review of the Literature
Authors: Delacruz Victor , Jorda Merce , Gomez-Fernandez Carmen , Benedetto Pasquale , Ganjei Parvin
Published: February 2021

Primary angiosarcoma of the spleen is a very rare neoplasm with a poor prognosis. The definitive diagnosis is usually based on the histologic evaluation of the splenectomy specimen. We describe a case of angiosarcoma diagnosed by fine-needle aspiration cytology prior to splenectomy. A 69-year-old white woman presented with heterogeneous lesions in the spleen during a follow-up computed tomographic scan for a history of liposarcoma of the right buttock. A malignant endothelial neoplasm was diagnosed by fine-needle aspiration cytology using immunocytochemistry, and a splenectomy confirmed the presence of angiosarcoma. To our knowledge, this is the first well-documented and confirmed case of primary angiosarcoma of the spleen diagnosed by fine-needle aspiration cytology. This report emphasizes the value of fine-needle aspiration cytology as an important diagnostic tool in splenic neoplasms.
Intratesticular Mucinous Cystadenoma: Immunohistochemical Comparison With Ovarian and Colonic Tissue
Authors: Alasio Teresa M. , Borin James , Taylor Kevia , Bar-Chama Natan , Unger Pamela D.
Published: February 2021

We report a case of a primary intratesticular mucinous cystadenoma in an asymptomatic 39-year-old man. The mass was found incidentally during a consultation for infertility. Pathologic examination of the orchiectomy specimen revealed a unilocular cyst lined with bland mucinous epithelium and mucinous extravasation, consistent with a diagnosis of mucinous cystadenoma. Foci of bone were also found in association with extensive chronic inflammation. Immunohistochemical stains performed showed immunoreactivity for cytokeratin 7, and nonreactivity for cytokeratin 20, CA125, chromogranin, and synaptophysin. The immunohistochemical staining patterns of the present case are compared with those of known mucinous cystadenomas of the ovary and nonneoplastic colonic mucosa. The histogenesis of this entity is discussed in light of the literature and the immunohistochemical findings in this rare case.
Detection of t(14;18)(q32;q21) in B-Cell Chronic Lymphocytic Leukemia
Authors: Kern Wolfgang , Haferlach Torsten , Schnittger Susanne , Schoch Claudia
Published: February 2021

Cytomorphologic testing and multiparameter flow cytometry are the mainstays in diagnosing B-cell chronic lymphocytic leukemia, whereas fluorescence in situ hybridization that targets the translocation t(14;18)(q32;q21) often is used to identify follicular lymphoma. Therapy is highly diverse between both diseases. We describe a case with cytomorphologically and immunologically proven B-cell chronic lymphocytic leukemia in which t(14;18)(q32;q21) was found.
Three-Dimensional Virtual Microscopy of Colorectal Biopsies
Authors: Wu Mark Li-cheng , Varga Viktor Sebestyen , Kamaras Viktor , Ficsor Levente , Tagscherer Attila , Tulassay Zsolt , Molnar Bela
Published: February 2021

Conventional optical microscopy of specimens from colorectal biopsies commonly produces diagnostic errors due to incomplete sampling or poor orientation. Obtaining additional sections or re-embedding may help avoid these errors, but can prolong turnaround time. We describe new technology, which incorporates exhaustive sectioning, 3-dimensional reconstruction, and virtual microscopy, that may eliminate these problems by enabling pathologists to rapidly examine entire specimens and convert poorly oriented mucosa to well-oriented mucosa.
An Unusual Case of Peripheral T-Cell Lymphoma With CD56 Positivity and Angiocentric, Angiodestructive Morphology Arising in the Ileum
Authors: Frank Matthew C. , Bono Erika , Sun Tsieh
Published: February 2021

Natural killer cell and cytotoxic T-cell lymphomas are frequently difficult to distinguish because they share many common features, and yet it is important to make an accurate diagnosis because their prognoses differ. We report an unusual case of a white man with a CD56-positive T-cell lymphoma in the ileum. The histologic pattern was characterized by angioinvasion and angiodestruction. Immunohistochemical staining showed positive reactions to CD3, CD8, CD43, CD45RO, CD56, and T-cell intracellular antigen-1, but negative reactions to CD4, CD5, CD20, CD23, and CD57. Epstein-Barr virus (EBV) was not detected by EBV–latent membrane protein staining and EBV polymerase chain reaction technique. The T-cell receptor γ chain gene was rearranged. According to the World Health Organization classification, the absence of EBV excludes the diagnosis of extranodal natural killer/T-cell lymphoma, nasal type. However, the association of EBV with this lymphoma in white patients is not clear. Therefore, absence of EBV alone does not necessarily exclude nasal-type natural killer/T-cell lymphoma, particularly because the histologic pattern in this case is highly characteristic of this tumor.
Immunohistochemical Expression of Cyclooxygenase 2 in Follicular Carcinomas of the Thyroid
Authors: Haynik Denise M. , Prayson Richard A.
Published: February 2021

Context.—Cyclooxygenase 2 (COX-2) has been shown to be up-regulated and/or overexpressed in a variety of human neoplasms. However, limited data exist on the role of COX-2 in follicular carcinomas of the thyroid. Studies in this area are potentially significant, since therapeutic agents that inhibit COX-2 are currently available and could play a role in treatment.

Design.—A retrospective clinicopathologic review with COX-2 immunohistochemical staining of 34 follicular carcinomas and 7 follicular adenomas with incomplete capsular penetration was performed.

Results.—The study included 41 patients (25 women; mean age, 50.9 years). All patients underwent gross total resection of the neoplasm. Fifteen carcinoma patients received adjuvant radiotherapy. Seven patients with follicular carcinomas developed recurrent disease: 3 patients were alive (mean follow-up, 10.1 years) and 4 patients died of metastatic disease (mean follow-up, 3.5 years). All remaining patients were disease free (mean follow-up, 5.9 years). Only 1 follicular adenoma with incomplete capsular penetration recurred (patient alive at 9 years). The remaining patients were disease free (mean follow-up, 4.9 years). The COX-2 staining was positive in 11 tumors (9 of 34 follicular carcinomas, 2 of 7 follicular adenomas with incomplete capsular penetration). A greater percentage of recurrences (36% COX-2 positive vs 13% COX-2 negative) and fatal tumors (18% COX-2 positive vs 7% COX-2 negative) occurred in patients who had COX-2–positive staining neoplasms.

Conclusion.—Only a few follicular carcinomas (26%) and follicular adenomas with incomplete capsular penetration (29%) express COX-2 by immunohistochemical analysis. The data suggest that such expression of COX-2 may correlate with increased tumor recurrence and death; however, studies with larger numbers of patients will be needed to establish this.
Intracranial Extension of Acinic Cell Carcinoma of the Parotid Gland
Authors: Spencer M. Loreto , Galvao Neto Antonio , Fuller Gregory N. , Luna Mario A.
Published: February 2021

We report the case of a 47-year-old woman who experienced multiple recurrences of acinic cell carcinoma, lung metastasis, and intracranial extension of the tumor during a 32-year period. In this report, the clinical, microscopic, histochemical, and electron microscopy features of this acinic cell carcinoma are described, and a review of published information about this neoplasm is presented.
Allergic Bronchopulmonary Aspergillosis: An Overview
Authors: Zander Dani S.
Published: February 2021

This article provides an overview of the major pathologic manifestations of allergic bronchopulmonary aspergillosis; patient characteristics; clinical, radiographic, and laboratory features of the disease; and current knowledge about its pathogenesis. Although allergic bronchopulmonary aspergillosis is an infrequent complication of asthma or cystic fibrosis, recognition of this disorder is important to avoid progression of bronchiectasis and lung parenchymal damage. Clinical, laboratory, and radiographic criteria allow for diagnosis of most cases, but the pathologist may encounter clinically unsuspected or atypical cases that require morphologic confirmation.
Coccidioidomycosis of the Tongue
Authors: Rodriguez Rafael A. , Konia Thomas
Published: February 2021

A Spanish-speaking farm worker with type 2 diabetes mellitus presented to our institution with an ulcerating tongue lesion. He was initially evaluated for possible squamous cell carcinoma; however, histologic examination revealed coccidioidomycosis. Coccidioidal titers were elevated and consistent with disseminated disease, although the patient had no systemic symptoms and clinical evaluation was negative. He was ultimately treated with intravenous and oral antifungal medication, which was followed by improvement of his tongue lesion.
Nodular Mucinosis of the Breast: A Case Report With Pathologic, Ultrasonographic, and Clinical Findings and Review of the Literature
Authors: Sanati Souzan , Leonard Morton , Khamapirad Tuenchit , Eltorky Mahmoud A.
Published: February 2021

Nodular mucinosis is an extremely rare breast lesion. This benign mass usually presents clinically as a poorly circumscribed, subareolar, myxoid mass in young female patients. We report a case of this rare breast lesion and discuss its clinical, radiologic, and histopathologic features. A 21-year-old white woman presented with a mass in the left breast of 6 months' duration. She had never been pregnant or had any history of breast feeding, surgery, trauma, or use of exogenous hormones or a family history of breast cancer. Clinical breast examination demonstrated a 1 cm “rubbery” mass directly under and continuous with the left nipple. The skin that covered the mass had an edematous and irregular appearance without erythema or drainage from the nipple. Ultrasonography demonstrated a 1-cm, nonintraductal, circumscribed, homogeneous, isoechoic mass that was continuous or part of the base of the left nipple. The mass was smooth, with a thin echogenic rim. Doppler flow showed some vascularity. These findings suggested a benign breast lesion, including a fibroadenoma or nipple adenoma. Despite reassurance, the patient desired excision of the lesion. Gross examination revealed a nodular, rubbery-firm, ovoid, pink, polypoid mass that measured 1.5 × 0.9 × 0.8 cm. Microscopic examination showed a well-circumscribed tumor with a nodular appearance, which consisted of an accumulation of pink myxoid tissue and contained spindle cells with bland-appearing nuclei, no mitosis, and mild cellularity. The pink myxoid tissue was stained with Hale colloidal iron and Alcian blue. The Alcian blue stain was removed by pretreatment with hyaluronidase. The spindle cells stained with vimentin and smooth muscle actin; however, they did not express smooth muscle myosin or cytokeratin. This report presents and discusses the pathologic, ultrasonographic, and clinical findings of this rare entity.
Cytologic Identification of Reinke Crystalloids in Scrapings and Imprints of Fresh Testicular Tumors: A Simple and Rapid Technique for Intraoperative Use
Authors: Hribar Kambridge P. , Warner Nancy E. , Sherrod Andy E.
Published: February 2021

Although not required for the diagnosis, crystalloids of Reinke are pathognomonic for Leydig cell tumor. However, conventional frozen section rarely reveals their presence. A method of rapid identification of crystalloids of Reinke could improve the intraoperative diagnosis. We tested the efficacy of touch imprints and scrape smears for the identification of crystalloids in 2 cases of Leydig cell tumor of the testis. Intraoperative smears of the tumors yielded abundant crystals. Scrape cytologic testing was the better method. We speculate that the process of scraping, and to a lesser extent touch imprinting, disrupts the cytoplasm of the Leydig cells and releases the crystalloids. We conclude that cytologic testing is an effective method of identifying crystalloids of Reinke in Leydig cell tumors of the testis.
Papillary Thyroid Carcinoma: An Overview
Authors: Al-Brahim Nabeel , Asa Sylvia L.
Published: February 2021

Papillary carcinoma is the most common malignant tumor of the thyroid. It has a variable macroscopic appearance that differs according to the variant microscopic morphologies and the presence or absence of degenerative changes. The histologic variants can be challenging to the pathologist, and some are of clinical significance because of prognostic implications. In this short review, we discuss an approach to papillary carcinoma, the diagnostic dilemmas and controversies, and the ancillary studies that are helpful in resolving them, including immunohistochemistry and molecular studies.
Polycythemia Vera: New Clinicopathologic Perspectives
Authors: Cao Ming , Olsen Randall J. , Zu Youli
Published: February 2021

Context.—Polycythemia vera (PV) is a clonal myeloproliferative disease characterized by an erythroid dominant trilineage proliferation of hematopoietic precursor cells. Classified as a chronic myeloproliferative disease, PV represents a histopathologic spectrum of 2 recognized stages, the polycythemic and postpolycythemic phase. The clinical manifestations of hemorrhage, thrombosis, and increased red cell mass are directly related to primary bone marrow dysfunction. Prognosis is strongly associated with thrombosis risk and disease progression; thus, treatment is directed toward minimizing coagulopathic complications and preventing leukemic transformation. Recently, a specific point mutation in the Janus kinase 2 (JAK2) gene was described in a majority of PV patients. The potential diagnostic and/or prognostic value of JAK2V617F is discussed.

Objective.—To review important developments from the recent and historical literature. Modern diagnostic criteria and emerging molecular findings are emphasized.

Data Sources.—A comprehensive review was performed of the relevant literature indexed in PubMed (National Library of Medicine) and referenced medical texts.

Conclusions.—Modified clinical, histologic, and laboratory criteria have clarified the diagnosis of PV. Also, continuing studies on the recently discovered JAK2V617F gene mutation may significantly improve our understanding of PV pathogenesis and facilitate its medical management.
Chronic Idiopathic Myelofibrosis: Clinicopathologic Features, Pathogenesis, and Prognosis
Authors: Ahmed Arsalan , Chang Chung-Che(Jeff)
Published: February 2021

Context.—Chronic idiopathic myelofibrosis (CIMF) is a clonal myeloproliferative disease characterized by panmyelosis with intact maturation, progressive bone marrow fibrosis, and multiorgan extramedullary hematopoiesis.

Objective.—This review article aims to summarize the recent updates regarding the clinicopathologic features, molecular pathogenesis, cytogenetic abnormalities, diagnostic criteria, new diagnostic ancillary tests, and prognostic factors of CIMF.

Data Sources.—Important relevant articles indexed in PubMed/MEDLINE (National Library of Medicine) through the end of 2005 and referenced medical texts.

Conclusions.—Because CIMF has a variety of clinical presentations, diagnosis may be challenging; the prefibrotic stage of CIMF has always been a challenging disease for pathologists to diagnose accurately. The recently proposed European Clinical and Pathological criteria can be helpful in the diagnosis of CIMF, especially in its prefibrotic stage. The enumeration of CD34-positive cells in the peripheral blood and the presence of circulating endothelial progenitor cells are the new important ancillary tests for the diagnosis of a small subset of patients with CIMF with atypical presentation. The recent discovery of the new mutation affecting the Janus tyrosine kinase 2 (JAK2V617F), more frequently observed in patients with polycythemia vera, is seen in approximately 35% to 57% of patients with CIMF. This mutation can serve as another diagnostic tool. Important factors affecting prognosis in CIMF are anemia, age of the patient, white blood cell count, degree of fibrosis, and number of blasts in the peripheral blood.
Mast Cell Quantification in Normal Peritoneum and During Peritoneal Dialysis Treatment
Authors: Jiménez-Heffernan JoséA. , Bajo M. Auxiliadora , Perna Cristian , del Peso Gloria , Larrubia Juan R. , Gamallo Carlos , Sánchez-Tomero JoséA. , López-Cabrera Manuel , Selgas Rafael
Published: February 2021

Context.—Mast cells (MCs) have been implicated in fibrogenesis, angiogenesis, and immunity against bacteria. These 3 mechanisms participate in the peritoneal pathology secondary to peritoneal dialysis (PD) treatment. Despite their potential relevance to PD-related pathology, few studies have focused on MCs.

Objective.—To evaluate possible variations in the number of MCs during PD treatment.

Design.—A quantitative study of tissue MCs in normal and pathologic peritoneum. Parietal peritoneal biopsies were collected from 4 groups: (1) normal controls (n = 9), (2) uremic non-PD patients (n = 16), (3) uremic patients on PD (n = 26), and (4) non-renal patients with inguinal hernia (n = 20). MCs were evaluated using immunohistochemistry for the detection of tryptase. The total number of cross sections of vessels per peritoneal field was examined in 22 of the 26 peritoneal biopsies of PD patients.

Results.—PD tissue samples showed fibrosis, mesothelial cell loss, and variable hyalinizing vasculopathy. The number of MCs was similar in normal controls and non-PD uremic patients (mean ± SE: 7.13 ± 0.67 and 7.74 ± 0.74 MCs/mm2, respectively). Peritoneal dialysis patients showed a reduction (4 ± 0.38 MCs/mm2, P < .001), whereas hernia sac samples showed an increase (10.59 ± 3.48 MCs/mm2). MC reduction showed no correlation with time on dialysis, fibrosis, number of vessels, or previous episodes of peritonitis.

Conclusions.—The peritoneum of patients receiving PD treatment shows a reduction of MCs. Despite such a reduction, fibrosis takes place, suggesting that MCs do not play a critical role in fibrosis genesis. Mast cell loss may be a contributory factor to peritonitis episodes in PD patients.
Nonsecretory Plasma Cell Myeloma—Becoming Even More Rare With Serum Free Light-Chain Assay: A Brief Review
Authors: Shaw Gene R.
Published: February 2021

Context.—Nonsecretory plasma cell myeloma is characterized by an absence of detectable monoclonal protein in both the serum and urine. It is generally reported to comprise approximately 1% to 5% of all cases of plasma cell myeloma and, because of its rarity, requires a high index of suspicion and bone marrow biopsy to establish the diagnosis.

Objective.—Review the diagnostic strategy when nonsecretory plasma cell myeloma is a clinical consideration in light of a relatively new serum free light chain assay.

Data Sources.—Case study and review of the literature.

Conclusions.—Initial data using a recently developed nephelometric serum free light chain assay suggests that only about one fourth of nonsecretory plasma cell myeloma cases may be truly nonsecretory. The definition of nonsecretory plasma cell myeloma should be modified to exclude cases with evidence of clonality using the serum free light chain assay.
The Significance of Certification in Liquid-Based Cytology and Performance in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytopathology
Authors: Renshaw Andrew A. , Mody Dina R. , Walsh Molly , Bentz Joel S. , Colgan Terence J.
Published: February 2021

Context.—Morphology training and certification provided by the manufacturer is required before laboratories are allowed to prepare and interpret liquid-based cytology (LBC) gynecologic slides. Whether this certification is associated with improved LBC interpretation performance is not known.

Objective.—To determine whether LBC certification correlates with performance.

Design.—The results of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytopathology for the year 2004 were reviewed. During this year a question on the answer form asked participants whether they were certified in LBC preparations. Participant responses were analyzed at 2 levels of agreement with the reference diagnosis of unknown glass slides mailed quarterly.

Results.—For cytotechnologists and pathologists, participants who were LBC certified had a significantly lower total discordant rate to series than participants who were not certified for validated LBC ThinPrep (Cytyc Corp, Marlborough, Mass) preparations (P < .001 for both groups). The results were similar for validated conventional preparations for pathologists but not for cytotechnologists. The differences were present across most individual diagnostic series. Differences were most striking for low-grade squamous intraepithelial lesions. In addition, cytotechnologists and pathologists who were certified had a significantly lower total discordant rate to the exact diagnosis for validated LBC ThinPrep slides than those who were not certified (discordant rates for cytotechnologists, 14.14% and 23.36%, respectively, P < .001; for pathologists, 15.99% and 24.07%, respectively, P < .001).

Conclusion.—Although not all confounding factors were excluded in this study, LBC certification is associated with a significantly lower discordant rate to both series and exact diagnosis for validated LBC ThinPrep preparations.
Practical Pathology of Gunshot Wounds
Authors: Denton J. Scott , Segovia Adrienne , Filkins James A.
Published: February 2021

Context.—Gunshot wounds are the most common cause of homicidal death in the United States. Analysis and interpretation of fatal gunshot wounds is an important and common practice among forensic pathologists. Additionally, for pathology residents, it is an integral aspect of their training during their rotations at medical examiner or coroner offices.

Objective.—The correct interpretation of gunshot wounds by forensic pathologists not only provides valuable information that can assist law enforcement in their investigation but also is essential for the final determination of manner of death. Discussion of the practical, basic, and essential skills required to interpret gunshot wounds include distinguishing a classic entrance wound from an exit wound; recognizing atypical entrance and exit wounds; utilizing the features of soot and stippling patterns to differentiate among contact, close, and distant range gunshot wounds; understanding of the trauma produced by gunshot wounds; and understanding the importance of recovering and documenting/handling any projectiles recovered at autopsy.

Data Sources.—This article reviews numerous standard forensic pathology textbooks and the pertinent literature to formulate practical guidelines to assist the pathologist in the performance of forensic autopsies and the investigation of gunshot wound fatalities.

Conclusions.—Pathologists who perform investigations and autopsies to determine the cause and manner of death in gunshot wound cases must be aware of the implications, requirements, and pitfalls in interpretation of the injuries so that the examination fulfills its expectations to the community and the justice system.
Distinct Expression Patterns of E-Cadherin and β-Catenin in Signet Ring Cell Carcinoma Components of Primary Pulmonary Adenocarcinoma
Authors: Moon Kyung Chul , Cho Soo Youn , Lee Hye Seung , Jeon Yoon Kyung , Chung Jin-Haeng , Jung Kyeong Cheon , Chung Doo Hyun
Published: February 2021

Context.—E-Cadherin and β-catenin complexes have been suggested to have critical roles in cancer development and progression. Primary signet ring cell carcinoma (SRCC) of the lung is a rare variant of pulmonary adenocarcinoma, and E-cadherin and β-catenin expressions of this tumor have not been documented, to our knowledge.

Objective.—To characterize the E-cadherin and β-catenin expressions in SRCC of the lung.

Design.—An immunohistochemical evaluation of E-cadherin and β-catenin expressions in 10 cases of SRCC of the lung, 10 cases of conventional pulmonary adenocarcinoma, 10 cases of gastric SRCC, and 10 cases of colorectal SRCC was performed.

Results.—Membranous E-cadherin and β-catenin expressions were frequently reduced or absent in all types of tumors tested. Aberrant E-cadherin localization and nuclear β-catenin accumulation were frequently found in gastric (6/10 and 5/10, respectively) and colorectal (7/10 and 9/ 10, respectively) SRCCs, whereas SRCC of the lung rarely showed aberrant E-cadherin localization (1/10) or nuclear β-catenin accumulation (0/10).

Conclusions.—Signet ring cell carcinoma of the lung rarely showed aberrant E-cadherin localization or β-catenin nuclear accumulation, which are frequent events in gastric and colorectal SRCCs. These results suggest that the biologic roles of E-cadherin and β-catenin complexes in SRCC of the lung differ from their roles in gastric or colorectal SRCCs.
Combination of D-Dimer and Amino-Terminal Pro-B-Type Natriuretic Peptide Testing for the Evaluation of Dyspneic Patients With and Without Acute Pulmonary Embolism
Authors: Melanson Stacy E. F. , Laposata Michael , Camargo, Jr Carlos A. , Chen Annabel A. , Tung Roderick , Krauser Dan , Anwaruddin Saif , Baggish Aaron , Cameron Renee , Sluss Patrick , Lewandrowski Kent B. , Lee-Lewandrowski Elizabeth , Januzzi James L.
Published: February 2021

Context.—D-dimer concentration can be used to exclude a diagnosis of acute pulmonary embolism. However, clinicians frequently order unnecessary supplemental testing in patients with low concentrations of D-dimer. Elevations in natriuretic peptides have also been described in the setting of pulmonary embolism.

Objective.—We investigated the integrative role of D-dimer with amino-terminal pro-B-type natriuretic peptide for the evaluation of patients with and without acute pulmonary embolism.

Design.—Patients were selected for analysis from a previous study in which levels of D-dimer and amino-terminal pro-B-type natriuretic peptide were measured. The presence of pulmonary embolism was determined by computed tomographic angiography.

Results.—The median levels of D-dimer were significantly higher in patients with acute pulmonary embolism. Similarly, the median levels of amino-terminal pro-B-type natriuretic peptide were higher in patients with pulmonary embolism.

Conclusions.—The Roche Tina-quant D-Dimer immunoturbidimetric assay provides a high negative predictive value and can be used to exclude acute pulmonary embolism in patients with dyspnea. Measurement of amino-terminal pro-B-type natriuretic peptide in addition to D-dimer improves specificity for acute pulmonary embolism without sacrificing negative predictive value. A combination of both markers may offer reassurance for excluding acute pulmonary embolism, and thus avoid redundant, expensive confirmatory tests.
Documentation of Surgical Specimens Using Digital Video Technology
Authors: Melín-Aldana Héctor , Carter Barbara , Sciortino Debra
Published: February 2021

Context.—Digital technology is commonly used for documentation of specimens in anatomic pathology and has been mainly limited to still photographs. Technologic innovations, such as digital video, provide additional, in some cases better, options for documentation.

Objective.—To demonstrate the applicability of digital video to the documentation of surgical specimens.

Design.—A Canon Elura MC40 digital camcorder was used, and the unedited movies were transferred to a Macintosh PowerBook G4 computer. Both the camcorder and specimens were hand-held during filming. The movies were edited using the software iMovie. Annotations and histologic photographs may be easily incorporated into movies when editing, if desired.

Results.—The finished movies are best viewed in computers which contain the free program QuickTime Player. Movies may also be incorporated onto DVDs, for viewing in standard DVD players or appropriately equipped computers. The final movies are on average 2 minutes in duration, with a file size between 2 and 400 megabytes, depending on the intended use. Because of file size, distribution is more practical via CD or DVD, but movies may be compressed for distribution through the Internet (e-mail, Web sites) or through internal hospital networks.

Conclusions.—Digital video is a practical, easy, and affordable methodology for specimen documentation, permitting a better 3-dimensional understanding of the specimens. Discussions with colleagues, student education, presentation at conferences, and other educational activities can be enhanced with the implementation of digital video technology.
“Benign,” Metastasizing Adenomyoepithelioma of the Breast: A Report of 2 Cases
Authors: Nadelman Celina M. , Leslie Kevin O. , Fishbein Michael C.
Published: February 2021

Adenomyoepitheliomas of the breast are rare tumors composed of a proliferation of 2 cell populations. For the most part, they are considered to be benign, but they locally recur. Those neoplasms that metastasize are deemed to have come from a histologically malignant primary tumor. Herein, we describe 2 cases of metastases of histologically “benign” adenomyoepitheliomas of the breast to the lung. In both cases, the primary neoplasms and the metastases did not show histologic features of malignancy. These unique cases represent another example of neoplasms that can metastasize in the absence of histologic features that would suggest malignant behavior. Establishing the diagnosis, determining optimal therapy, and predicting outcome are problematic because of the rarity of this entity. Perhaps, classification of adenomyoepitheliomas should be changed to recognize those neoplasms with malignant behavior.
Are Gadolinium-Based Contrast Media Nephrotoxic?: A Renal Biopsy Study
Authors: Akgun Hulya , Gonlusen Gulfiliz , Cartwright, Jr Joiner , Suki Wadi N. , Truong Luan D.
Published: February 2021

Gadolinium-based contrast media were originally introduced as alternatives to iodinated media for magnetic resonance imaging. Although originally thought to be nonnephrotoxic, gadolinium-based contrast media have recently been reported to be associated with acute renal failure; the mechanism and the underlying renal injury are not completely understood. We report what is, to our knowledge, the first renal biopsy in this context. A 56-year-old patient underwent 2 consecutive vascular imaging procedures in conjunction with gadolinium-based contrast medium administration. A few days later, the patient developed acute renal failure. A renal biopsy showed acute tubular cell injury including patchy tubular cell necrosis, tubular cell degeneration, and marked proliferation of tubular cells, together with mild interstitial edema and interstitial inflammation, but without significant glomerular or vascular changes. During supportive therapy, renal function was partially regained. This case emphasizes the potential nephrotoxicity of gadolinium-based contrast media and suggests that the nephrotoxicity is related to potentially reversible acute tubular cell injury.
Prognostic Significance of Histomorphologic Parameters in Diffuse Malignant Peritoneal Mesothelioma
Authors: Cerruto Carlos A. , Brun Erwin A. , Chang David , Sugarbaker Paul H.
Published: February 2021

Context.—Diffuse malignant peritoneal mesothelioma is currently regarded as a rare and lethal primary tumor arising from the peritoneal membrane. In the past, treatment plans with variable combinations of surgery and systemic chemotherapy were associated with a median survival of approximately 1 year. Standardized treatments using cytoreductive surgery and perioperative intraperitoneal chemotherapy have extended this survival.

Objective.—To critically analyze the prognostic significance of histomorphologic parameters as a determinant of survival.

Design.—Sixty-two consecutive patients with diffuse malignant peritoneal mesothelioma in whom data were prospectively accumulated were retrospectively analyzed by 14 different histomorphologic parameters. The influences of these pathologic characteristics on survival were critically statistically evaluated.

Results.—In a univariate analysis, histologic type, nuclear/nucleolar size, stroma, depth of invasion into the bowel, atypical mitoses, mitotic index, necrosis, lymph node involvement, and chromatin patterns were found to be significant. In the multivariate analysis, histologic type and nuclear/nucleolar size remained as determinant histomorphologic characteristics. Use of biphasic/sarcomatoid histologic type as a poor prognostic characteristic was limited in that only 8% of patients showed this histology.

Conclusions.—Histomorphologic parameters carry prognostic significance in predicting the survival of patients with diffuse malignant peritoneal mesothelioma when treated in a standardized fashion using cytoreductive surgery and perioperative intraperitoneal chemotherapy. Nuclear/nucleolar size was found to be a reliable histomorphologic assessment available to assess prognosis in these patients.