bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Epstein-Barr Virus–Associated Hodgkin Disease of the Ileum Complicating Crohn Disease
Authors: Li Shiyong , Borowitz Michael J.
Published: January 2021

We describe a case of primary Hodgkin disease of the terminal ileum in a 38-year-old man with Crohn disease of 24 years' duration. The infiltrate was located in an ulcerated fistula involving the terminal ileum and urinary bladder. Reed-Sternberg cells and their variants were characteristically positive for CD15, fascin, and CD30 and showed focal positivity for CD20. Epstein-Barr virus messenger RNA was also detected in the neoplastic cells. Staging revealed no evidence of other lymph node or organ involvement. Although rare, primary gastrointestinal Hodgkin disease arising in the setting of Crohn disease may have a stronger association with Epstein-Barr virus infection than conventional Hodgkin disease.
Reference Laboratory Telephone Service Quality
Authors: Dale Jane C. , Novis David A. , Meier Frederick A.
Published: January 2021

Objectives.—To establish the rates with which reference laboratories resolve inquiries telephoned to them from primary laboratories and to identify reference laboratory practices associated with higher rates of inquiry resolution.

Design and Participants.—For 2 months, or until 50 contacts had occurred, 545 primary laboratories participating in the College of American Pathologists Q-Probes laboratory quality improvement program prospectively documented and characterized telephone inquiries they made to a reference laboratory of their choice. Participants also cataloged their own laboratory's demographic and practice characteristics and their reference laboratory's customer service characteristics.

Main Outcome Measure.—Rates with which reference laboratories resolved telephone inquiries.

Results.—Participants characterized 11 031 (78.7%) of 14 017 telephone inquiries as resolved by the reference laboratories. Ranked according to inquiry resolution rates, primary laboratories in the 90th percentile characterized reference laboratories as resolving 100% of their inquiries; those in the 10th percentile characterized reference laboratories as resolving only 54.2% of their inquiries. The rate of resolved inquiries was significantly higher (P = .0047) for participants using reference laboratories with 24-hour customer service than it was for participants using reference laboratories with less than 24-hour service. Most primary laboratories (80.9%) chose to monitor 1 of 11 national reference laboratories; in this subset, median rates of inquiry resolution ranged from 90.2% to 55.0% (P < .0001), despite no significant variation in other measured customer service characteristics.

Conclusions.—Primary laboratories experience significant differences in the rates with which reference laboratories resolve telephone inquiries. The performance benchmark for reference laboratories is resolution of at least 90% of telephone inquiries from primary laboratory customers.
An Immunostaining Panel for Diagnosis of Malignancy in Mucinous Tumors of the Pancreas
Authors: Zhao Jin , Liang Sharon X. , Savas Lou , Banner Barbara F.
Published: January 2021

Background.—The diagnosis of malignancy in pancreatic mucinous cystic tumors depends on demonstrating invasion that may be focal and require extensive sectioning.

Objective.—To explore markers that may indicate malignant potential in mucinous cystic tumors.

Design.—Routinely processed sections from resected specimens of 12 normal pancreata, 14 pancreata with chronic pancreatitis, 9 mucinous cystic tumors, and 30 invasive adenocarcinomas were immunostained with antibodies to p53, HER-2/neu, epithelial growth factor receptor (EGFR), transforming growth factor α (TGF-α), and Ki-67.

Results.—Expression of p53, HER-2/neu, and Ki-67 was significantly more frequent in mucinous tumors than in normal pancreatic tissue and chronic pancreatitis tissue (P = .0003 to .05). Strong expression (more than one third of cells positive) and strong intensity (2+ and 3+) of staining of p53 and EGFR were seen only in carcinomas. Coexpression of p53/HER-2/neu and EGFR/HER-2/neu and a frequency of Ki-67+ nuclei of greater than 5% of cells discriminated between mucinous tumors and normal pancreatic tissue and chronic pancreatitis tissue. p53 expression was significantly more frequent in carcinomas than in mucinous tumor (P = .0326). Coexpression of p53/EGFR discriminated between mucinous tumors and carcinomas; however, TGF-α was not discriminative.

Conclusions.—The immunostaining panel of p53, HER-2/neu, Ki-67, and EGFR can be helpful in indicating malignant potential in mucinous tumors of pancreas in routine pathology practice.
Squamous Cell Carcinoma Detected by High-Molecular-Weight Cytokeratin Immunostaining Mimicking Atypical Fibroxanthoma
Authors: Gray Yulia , Robidoux Henry J. , Farrell David S. , Robinson-Bostom Leslie
Published: January 2021

Atypical fibroxanthoma can mimic other tumors, particularly spindle cell squamous cell carcinoma and spindle cell or desmoplastic melanoma. We describe a patient with chronic lymphocytic leukemia who developed acantholytic squamous cell carcinoma on the face, which recurred and metastasized to a cervical lymph node. This tumor was at first diagnosed as atypical fibroxanthoma because of its histologic and immunostaining similarity. It showed weak or negative keratin cocktail staining and strong vimentin staining. However, a recurrent tumor was immunostained for high-molecular-weight keratin and showed strong positivity. Aggressive behavior of this squamous cell carcinoma may be due to altered immune response secondary to chronic lymphocytic leukemia.
Pigmented Pleomorphic Xanthoastrocytoma
Authors: Sharma Mehar Chand , Arora Rina , Khanna Navin , Singh Virender Pal , Sarkar Chitra
Published: January 2021

We describe a rare case of melanotic pleomorphic xanthoastrocytoma in a 32-year-old man who presented with partial complex seizures. Radiologically, the mass was located in the medial temporal lobe and was solid and cystic. Microscopic examination revealed features of a pleomorphic xanthoastrocytoma with some heavily pigmented cells. The pigment was demonstrated to be melanosomal melanin, which was confirmed by special stains, immunohistochemistry, and electron microscopy.
Spindle Cell Lipoma of the Parotid
Authors: Fasig John H. , Robinson Robert A. , McCulloch Timothy M. , Fletcher Mavis S. , Miller Carolyn K.
Published: January 2021

A 47-year-old man presented to the otolaryngologist with a 7-year history of a mass of the cheek. Fine-needle aspiration revealed foci of spindled cells admixed with abundant fat and myxoid material. A diagnosis of spindle cell lipoma was rendered on the resected specimen. The cytologic findings of spindle cell lipoma of the parotid gland as seen by fine-needle aspiration are presented along with the histologic correlates.
The Prognostic Significance of DNA Topoisomerase II-alpha (Ki-S1), p21/Cip-1, and p27/Kip-1 Protein Immunoexpression in Oligodendrogliomas
Authors: Korshunov Andrey , Golanov Andrey
Published: January 2021

Objective.—To evaluate a possible association between clinical outcome of patients with oligodendroglioma and expression of 2 cyclin-dependent kinase inhibitors, p21/Cip-1 (p21) and p27/Kip-1 (p27), and of DNA topoisomerase II-alpha (Ki-S1), which has been recently used as a marker of cellular proliferation.

Design.—Ninety-one specially selected patients with cerebral oligodendrogliomas treated with surgery and radiotherapy were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to p21, p27, and Ki-S1. A computerized color image analyzer was used to count immunostained nuclei.

Results.—The mean Ki-S1 labeling index (LI) was found to be significantly prominent for World Health Organization (WHO) high-grade tumors (9.5% vs 3.2% for WHO low-grade tumors). In contrast, the mean p27 LI was significantly higher for low-grade tumors (43.3% vs 25.7% for high-grade tumors). The number of p21-positive cases and the mean p21 LI were found to be relatively equal for low- and high-grade tumors. For low-grade oligodendrogliomas, the progression-free and overall survival times were found to be significantly shorter for tumors with p27 LIs less than 20%. For high-grade oligodendrogliomas, survival times were significantly reduced for tumors with Ki-S1 LIs greater than 10%. Regression-tree analysis identified 4 groups of oligodendrogliomas with distinctly different outcomes: (1) 32 patients with low-grade tumors and p27 LIs greater than 20%; (2) 14 patients with low-grade tumors and p27 LIs less than 20%; (3) 25 patients with high-grade tumors and Ki-S1 LIs less than 10%; and (4) 20 patients with high-grade tumors and Ki-S1 LIs greater than 10%.

Conclusions.—Immunoreactivity for Ki-S1 and p27 was found to be useful for further subdividing oligodendroglioma prognoses among low-grade and high-grade tumors. It seems unlikely that p21 immunohistochemistry will be of value for determining clinical outcomes for patients with oligodendrogliomas.
Low-Grade B-Cell Lymphoma With Coexpression of Both CD5 and CD10
Authors: Barekman C. L. , Aguilera N. S. I. , Abbondanzo S. L.
Published: January 2021

The coexpression of CD5 and CD10 has previously been reported in cases of intermediate- and high-grade lymphomas and in precursor B cells in normal or regenerating bone marrow. We report 3 cases of low-grade B-cell lymphoma that were found to coexpress CD5 and CD10 at the time of initial diagnosis. The first case was classified as small lymphocytic lymphoma; the second as follicle center lymphoma, follicular grade 1; and the third as small B-cell lymphoma otherwise not specified. Currently, the clinical implication of the coexpression of CD5 and CD10 is not known. We describe this finding to highlight the difficulty that may be encountered in classifying lymphomas in cases where this coexpression is present.
Metastatic Carcinomatous Cirrhosis and Hepatic Hemosiderosis in a Patient Heterozygous for the H63D Genotype
Authors: Mitchell Mark L. , Filippone Marciana D. , Wozniak Timothy F.
Published: January 2021

A 38-year-old woman had a mastectomy for infiltrating ductal carcinoma of the breast 3 years before her last admission and had received chemotherapy for known liver metastases. She developed the rapid onset of liver failure with portal hypertension and died in a hospice. Autopsy revealed macronodular cirrhosis of the liver secondary to metastatic carcinoma of the breast with associated florid fibrosis. This rare lesion, previously called metastatic carcinomatous cirrhosis, was also found, in this case, to have marked hepatic hemosiderosis, and analysis of the patient's DNA showed heterozygosity for the H63D genotype. The possibility of cirrhosis-associated hemosiderosis secondary to an iron metabolism abnormality associated with the H63D mutation of the HFE gene is proposed. Computed tomographic scans showed the development of cirrhosis during the 3-month period before the patient's last admission and suggested the possibility of a postnecrotic type origin.
Differential Expression ofrasSignal Transduction Mediators in Verrucous and Squamous Cell Carcinomas of the Upper Aerodigestive Tract
Authors: Lessard Julie L. , Robinson Robert A. , Hoffman Henry T.
Published: January 2021

Context.—ras gene mutations and expression of its gene product have been described in verrucous and squamous cell carcinomas. Other downstream signal-transduction mediators, extracellular signal-regulated kinases 1 and 2 (ERK-1 and ERK-2) and Raf-1, have not yet been as extensively studied.

Objective.—To determine patterns of expression of ERK-1, ERK-2, and Raf-1 in verrucous and squamous cell carcinomas of the upper aerodigestive tract.

Design.—Seventeen verrucous carcinomas and 10 squamous cell carcinomas of the upper aerodigestive tract were examined for the immunohistochemical expression of ERK-1, ERK-2, and Raf-1 product.

Results.—Raf-1 expression was intensely expressed in the most basal portions of the epithelium in verrucous carcinomas, but was minimally expressed in the suprabasalar areas. Anti-Raf-1 staining of the squamous cell carcinomas was diffuse and patchy throughout the tumor cells and was weak in intensity. There was no geographic preference of staining. The cytoplasmic expression of both ERK-1 and ERK-2 was predominantly negative in the most basal layers of the epithelium in the verrucous carcinomas, but was positive in the suprabasalar region of the epithelium. Immunohistochemical expression of ERK-1 and ERK-2 in the squamous carcinomas was diffuse throughout the tumor.

Conclusion.—There is strong correlation of the geographic expression of these mediators of ras signal transduction in verrucous and squamous carcinomas, but the cause of these differences remains unclear at present. The expression of these mediator proteins may have potential for diagnosis, as well as in understanding the biologic behavior of these lesions.
The Role of Fine-Needle Aspiration Biopsy in the Diagnosis and Management of Juvenile Hemangioma of the Parotid Gland and Cheek
Authors: Khurana Kamal K. , Mortelliti Anthony J.
Published: January 2021

Background.—The current recommendation for the management of juvenile hemangiomas (JH) is to delay treatment in the hope of spontaneous regression. However, accurate diagnosis is necessary before considering conservative management. Traditionally, the diagnosis of JH has required excisional biopsy. The cytology literature on this relatively rare neoplasm is sparse.

Objective.—To present our experience with fine-needle aspiration in the diagnosis and management of JH.

Design.—Three cases with a cytologic diagnosis consistent with JH of the parotid gland and cheek were identified from our cytopathology files. Aspirate smears, immunohistochemical studies, computed tomographic scan findings, and clinical follow-up were reviewed.

Results.—Patients were female infants ranging in age from 3 to 9 months and presented with an oval firm mass (size range, 2.0–5.0 cm) involving the parotid gland (2 cases) and cheek (1 case). Computed tomographic scan with contrast demonstrated homogeneous enhancement. Aspirate smears revealed spindle-shaped cells in sheets and clusters in a background of blood. The parotid gland aspirates and cell block preparations revealed ductal structures entrapped in sheets of spindle-shaped cells. Immunohistochemical studies revealed prominent vascular spaces lined by CD34 and factor VIII–positive flattened endothelial cells. The diagnosis of JH was rendered on the basis of the cytologic findings in conjunction with the radiologic and clinical findings. On clinical follow-up (8–24 months), none of the patients has shown any progression of the lesion.

Conclusions.—Fine-needle aspiration, in conjunction with imaging studies, is a useful tool in the diagnosis and management of JH. It eliminates the need for surgical excision for diagnostic purposes and allows for clinical follow-up of patients with JH.
Pseudopapillary Solid Cystic Tumor Arising From an Extrapancreatic Site
Authors: Fukunaga Masaharu
Published: January 2021

A case of pseudopapillary solid cystic tumor arising in the omentum of a 46-year-old woman is presented. A well-defined, encapsulated tumor measuring 5.2 × 4.0 × 4.0 cm was histologically characterized by a combination of solid and pseudopapillary growth patterns of tumor cells with abundant pale-to-eosinophilic cytoplasm. No pancreatic tissue was observed within or adjacent to the tumor. Immunohistochemically, the tumor was positive for vimentin, epithelial membrane antigen, and α1-antichymotrypsin. Ultrastructurally, the tumor cells contained electron dense granules of variable sizes, most likely representing lysosomes. Flow cytometry showed a diploid DNA content with a high S-phase fraction. The patient was well without recurrence 3 months after diagnosis. It is important to include pseudopapillary solid cystic tumor in the differential diagnosis of omental tumors.
Is the Human Papillomavirus Test in Combination With the Papanicolaou Test Useful for Management of Patients With Diagnoses of Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions?
Authors: Lee Nak-Woo , Kim Daesu , Park Jong-Tae , Kim Aeree
Published: January 2021

Objective.—To determine whether human papillomavirus (HPV) testing is useful in the evaluation of patients diagnosed with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) and whether the HPV test is appropriate as an alternative screening method.

Design.—The results of Papanicolaou (Pap) tests and subsequent hybrid capture tube (HCT) II tests for high-risk–type HPV were analyzed for 457 patients. Among these tests, 208 histologic diagnoses were made and correlated with the results of Pap and HPV tests. The sensitivity and specificity of the Pap test, HPV test, and the combined method of Pap and HPV tests to detect cervical intraepithelial neoplasia (CIN) 2/3 and all CIN were also measured.

Results.—Sixty (63.8%) of 94 women with LSIL and 31 (26.3%) of 118 women with ASCUS tested positive for high-risk HPV. The sensitivity values for Pap tests in detecting all cases of CIN and CIN 2/3 were 91.4% and 92.9%, respectively. The sensitivity values of HCT II tests using the high-risk probe for detecting all cases of CIN and CIN 2/3 were 62.6% and 88.1%, respectively. Biopsies confirmed that 10 (22.7%) of 44 LSIL patients with high-risk HPV had CIN 2/3, but only 1 (4.5%) of 22 LSIL patients without high-risk HPV had CIN 2/3.

Conclusion.—Testing for high-risk HPV with the HCT II test is useful in the detection of CIN 2/3 in LSIL groups and in the selection of patients for colposcopy in ASCUS groups, but it is not suitable for cervical cancer screening tests.
Hodgkin Lymphoma in a Renal Transplant Recipient Associated With Low Peripheral Blood Epstein-Barr Virus Genome Copies
Authors: Craver Randall D. , Scheer Wm Douglas , Correa Hernan , Vehaskari V. Matti , Yu Lolie C.
Published: January 2021

Posttransplant lymphoproliferative disorders are often accompanied by >500 Epstein-Barr virus (EBV) genome copies/105 lymphocytes, and they occur shortly after transplantation. Hodgkin lymphoma occurs rarely after transplantation, appearing a mean of 4.2 years posttransplant, and although Hodgkin lymphoma has strong associations with EBV, no quantitative analysis of peripheral blood EBV genome copies has been reported. A mixed cellularity Hodgkin lymphoma developed in a 17-year-old boy 4 years after a renal transplant. Serial EBV genome copy numbers from blood by competitive polymerase chain reaction had been obtained to assess for lymphoproliferative disease. Epstein-Barr virus genome copy numbers peaked at 500 copies/105 lymphocytes 8 months prior to Hodgkin lymphoma diagnosis but fell to 8 copies/105 lymphocytes at diagnosis. Reliance on EBV levels greater than 500 copies may result in delay of biopsy and diagnosis of Hodgkin disease in the posttransplant setting.
A Potential Source of False-Positive Sentinel Nodes
Authors: Chiu April , Hoda Syed A. , Yao Davis X. , Rosen Paul P.
Published: January 2021

The clinical and pathologic aspects of sentinel lymph node biopsy have generated much attention. Pitfalls in the pathologic handling of sentinel lymph node specimens have received little attention. We report a case in which a false-positive diagnosis might have been rendered on a sentinel lymph node because of an inadvertent immunostaining error. Attention was drawn to the problem by an unusual pattern of distribution of immunoreactive cells—which proved to be plasma cells rather than metastatic carcinoma cells.
Down-Regulation of Fas Expression in the Lymph Nodes of Patients Infected With Human Immunodeficiency Virus
Authors: Wang Liqiang , Adegboyega Patrick A.
Published: January 2021

Context.—The mechanism by which human immunodeficiency virus 1 (HIV-1) infection causes increased rates of apoptosis and gradual chronic depletion of CD4+ T lymphocytes in patients infected with HIV-1 is not known. Findings from in vitro culture studies and analysis of mononuclear cells in the peripheral blood of HIV-infected patients have led to the hypothesis that abnormal expression and/or interaction of Fas and Fas ligand (FasL) may play significant roles in the derangement of homeostasis of CD4+ lymphocytes in patients infected with HIV-1.

Objective.—To determine the in situ expression of Fas and FasL in the lymph nodes of patients infected with HIV-1.

Design.—Immunohistochemical expression of Fas and FasL was studied in the lymph node biopsy specimens from 20 patients infected with HIV-1. As controls, we also studied 120 lymph nodes from 28 HIV-1–seronegative patients with reactive lymphadenopathy.

Results.—In the reactive lymph nodes of seronegative patients, expression of Fas was diffuse in the germinal centers and also in immunoblast-like cells in the T-cell regions. In the lymph nodes of patients infected with HIV, there was a consistent remarkable decrease in Fas expression in 12 of 20 patients and a total lack of Fas expression in the remaining 8 patients. Expression of FasL was comparable in both patient groups.

Conclusions.—There is marked down-regulation of Fas in the lymph nodes of HIV-infected patients, a sharp contrast to what occurs in circulating mononuclear cells in the peripheral blood of these patients. These results indicate the need for further studies of this molecular event for possible therapeutic intervention based on reconstitution of Fas and/or FasL activity in the treatment of HIV infection.
Expression of E-Cadherin and p53 Proteins in Human Soft Tissue Sarcomas
Authors: Yoo Jinyoung , Park Sonya , Kang Chang Suk , Kang Seok Jin , Kim Byung Kee
Published: January 2021

Objective.—To investigate the expression of E-cadherin in human soft tissue sarcomas and its potential relationship to p53 alterations.

Design.—Tissue sections of 91 soft tissue sarcomas were analyzed by immunohistochemistry for E-cadherin and p53 proteins. Sixty-one tumors were investigated further by the application of the polymerase chain reaction technique and a direct sequence analysis procedure of exons 5 through 8 in the p53 gene.

Setting.—Tertiary-care teaching hospital.

Patients.—Ninety-one patients with soft tissue tumor were treated surgically. Thirteen of these patients had tumors with epithelial differentiation.

Results.—E-Cadherin was expressed at the cell-cell boundaries in 11 samples (12%): 9/13 (69%) with and 2/78 (3%) without histologic evidence of epithelial elements. Other sarcomas were completely negative for E-cadherin. Overexpression of p53 was detected in 30 cases (33%), 7 of which also demonstrated mutations in the p53 gene. The frequencies of p53 abnormalities in tumors with and without epithelial components were 8% and 37%, respectively. No association was established between E-cadherin immunoreactivity and p53 abnormalities (P = .13). Tumor grade strongly correlated with p53 alterations (P = .01), but not with E-cadherin expression (P = .07).

Conclusions.—These data support the involvement of p53 alterations in the pathogenesis of soft tissue sarcomas. The lack of E-cadherin expression in these tumors, with the exception of lesions showing epithelial differentiation, indicates that E-cadherin is not an important factor involved in cell-cell adhesion in sarcomas. It is, however, suggested that E-cadherin may play a role in the development and/or maintenance of epithelial architecture in sarcomas, regardless of p53 status.
Methotrexate-Related Nonnecrotizing Multifocal Axonopathy Detected by β-Amyloid Precursor Protein Immunohistochemistry
Authors: Moore Brian E. , Somers Nathan P. , Smith Thomas W.
Published: January 2021

We describe a 64-year-old woman with biphenotypic leukemia involving the meninges who received 2 doses of intrathecal methotrexate. Soon after treatment, the patient developed postural rigidity and a marked decline in mental status. The patient died of respiratory failure 1 month after methotrexate treatment was initiated. At autopsy, the brain was grossly normal. Routine microscopy showed no evidence of leukemic infiltrates or necrotizing lesions. However, when stained with β-amyloid precursor protein, multifocal axonal injury was evident in the brain, spinal cord, and nerve roots. Our findings show that immunohistochemical staining for β-amyloid precursor protein can effectively demonstrate axonal injury associated with methotrexate neurotoxicity, even when conventional staining procedures are negative. This technique may therefore reveal a possible pathologic substrate for some of the neurological complications seen in patients with methotrexate neurotoxicity.
Bronchial Carcinoid Tumor With Crystalloid Cytoplasmic Inclusions
Authors: Grogg Karen L. , Padmalatha Chandrashekar , Leslie Kevin O.
Published: January 2021

We report a bronchial carcinoid tumor with distinctive, cytoplasmic, rod-shaped crystalloid inclusions that were visible by light microscopy. These cytoplasmic structures were immunoreactive with antibodies against chromogranin A and synaptophysin in paraffin-embedded tissue. Ultrastructural studies showed them to be paracrystalline in nature and located within lysosomes. This case highlights an interesting, and potentially confusing, histologic manifestation in an otherwise typical bronchial carcinoid tumor.
Fine-Needle Aspiration Biopsy Diagnosis of “Invasive” Temporomandibular Joint Pigmented Villonodular Synovitis
Authors: Shapiro Steven L. , McMenomey Sean O. , Alexander Priscilla , Schmidt Waldemar A.
Published: January 2021

The clinical and aspiration cytologic details of a case of temporomandibular joint pigmented villonodular synovitis are presented and correlated with imaging, surgical, histopathologic, and clinical follow-up findings; the origin of such lesions is discussed. The lesion originally presented in a 36-year-old, otherwise healthy, white man as a unilateral mass involving the temporal fossa and temporomandibular joint region. The tumor's extent was defined by magnetic resonance imaging and computed tomographic scan; there was destruction of the temporomandibular joint and erosion of the temporal cranial bones by a lesion whose maximum dimensions were estimated by imaging to be 2.75 × 3.25 cm. The lesion was initially sampled and classified by computed tomography–guided fine-needle aspiration biopsy. Following complete resection, the original diagnosis was confirmed with both hematoxylin-eosin–stained paraffin sections and immunohistochemical staining. The patient remains free of disease 7 years postoperatively.
Morphologic Spectrum of Estrogen Receptor–Negative Breast Carcinoma
Authors: Scawn Richard , Shousha Sami
Published: January 2021

Context.—Estrogen receptor (ER)-negative breast carcinomas are a heterogeneous group of breast cancers that are generally thought to be aggressive.

Objective.—To determine the morphologic and immunohistochemical spectrum of a consecutive series of ER-negative breast carcinomas, in an attempt to understand the pathogenesis and behavior of these lesions.

Design.—Seventy-four consecutive cases of ER-negative invasive carcinomas were studied. Hematoxylin-eosin–stained sections were reviewed, and new sections were stained for c-erbB-2, p53, vimentin, and androgen and prolactin receptors. The findings were correlated with the axillary lymph node status as a measure of tumor aggressiveness.

Setting.—The histopathology department of a tertiary referral teaching hospital.

Results.—The tumors included 50 (68%) invasive ductal carcinomas, 21 (28%) medullary/atypical medullary carcinomas, and 1 each of invasive lobular, apocrine, and papillary carcinoma. Some of the invasive ductal cases had distinctive features that are described in this report. Maximum tumor diameter varied between 5 and 100 mm. Sixty tumors (81%) were grade 3, 13 (18%) were grade 2, and 1 (1%) was grade 1. Of the 60 cases in which the axillary node status was known, 34 (57%) had metastases, and 26 did not. Tumors associated with positive nodes were significantly larger than those associated with negative nodes (37.2 vs 17.8 mm, P < .001). A higher percentage of node-negative tumors were c-erbB-2 positive (42% vs 21%, P < .05). There were no differences between the 2 groups with regard to histologic type, tumor grade, or the expression of p53, vimentin, or androgen or prolactin receptors

Conclusions.—Many ER-negative breast carcinomas have distinctive microscopic features. Not all ER-negative tumors are aggressive, as judged by the absence of lymph node metastases in 43% of cases in this series. Tumor size is the most important indicator for the likelihood of the presence of lymph node metastases. The wide range of tumor sizes encountered in this series suggests that the ER status of a tumor is determined early in its natural history and supports the existence of 2 separate pathways for the development of ER-negative and ER-positive breast carcinomas.
Extranodal Posttransplant Plasmacytic Hyperplasia With Subsequent Posttransplant Plasmacytic Malignancy
Authors: Dunphy Cherie H. , Galambos Csaba , Polski Jacek M. , Evans H. Lance , Gardner Laura J. , Grosso Leonard E. , Montone Kathleen T.
Published: January 2021

Posttransplant lymphoproliferative disorders (PTLDs) represent a morphologic, immunophenotypic, and genotypic spectrum of disease. Most recently, Knowles et al divided PTLDs into 3 distinct categories: (1) plasmacytic hyperplasia, (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma, and (3) immunoblastic lymphoma and multiple myeloma. Although one form of PTLD may progress to another form, only 1 previous case has been reported in which multiple myeloma developed 14 months after an original diagnosis of plasmacytic hyperplasia. The type of solid organ transplant was not specified in that case. We report a post–cardiac transplant plasmacytic hyperplasia developing 7 years posttransplant. Six years subsequent to the plasmacytic hyperplasia, the patient developed a posttransplant plasmacytic malignancy, supported by morphology, flow cytometric immunophenotyping, and genotypic studies. Since we have no data to support disseminated bony disease or an abnormal serum protein, we have not used the term “multiple myeloma” for this case.
Malignant Intrahepatic Biliary Papillomatosis Associated With Viral C Cirrhosis
Authors: Mourra Najat , Hannoun Laurent , Rousvoal Geraldine , Parc Rolland , Flejou Jean-Francois
Published: January 2021

Biliary papillomatosis is a rare entity characterized by multiple papillary adenomas involving extensive areas of the biliary tract with a great potential for recurrence and malignant transformation. It has been reported in association with Caroli disease and a choledochal cyst. We report herein a case of malignant intrahepatic biliary papillomatosis associated with cirrhosis secondary to hepatitis C. To the best of our knowledge, this is the first report of this association.
Coronary Angiographic Findings in Patients With Clinical Unstable Angina According to Cardiac Troponin I and T Concentrations in Serum
Authors: Panteghini Mauro , Cuccia Claudio , Pagani Franca , Turla Claudia , Bonetti Graziella , Bonini Elena
Published: January 2021

Context.—Elevated cardiac troponin levels have been reported to identify unstable angina patients at high risk.

Objective.—To examine the relation of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels to findings of coronary angiography in these patients.

Methods.—Samples for troponin estimation were taken every 4 hours throughout the first 48 hours after admission before angiography in 34 patients with primary unstable angina. Patients were considered to be troponin positive if the marker was increased (>0.04 μg/L for cTnT and >0.03 μg/L for cTnI) in at least one sample collected.

Results.—An increased troponin (I or T) concentration was documented in 14 patients (41.2%). Twelve patients (35.3%) had elevations of both markers, whereas the remaining 2 patients had elevations of cTnI or cTnT alone. Patients with or without increased troponin levels did not differ with respect to degree of coronary disease at angiography. However, patients with elevated troponin concentrations had more complex lesion characteristics. In 69% of patients with increased cTnI levels and in 77% of patients with increased cTnT levels, type B2 or C lesions were documented with presence of ulcerated plaques and thrombus formation. In contrast, only 23% of the patients with elevated cTnI or cTnT levels had type A lesions compared with 71% of patients with negative troponin concentrations.

Conclusions.—Patients with unstable angina who have significant release of cTnI and/or cTnT have evidence of more complex lesions on coronary angiography, supporting the hypothesis that both troponins might be used without distinction as surrogate markers for microembolization from thrombus formation on a disrupted plaque.
Plasma Cell Granuloma of the Thyroid
Authors: Martinez Fernando , Filipowicz Ewa , Hudnall S. David
Published: January 2021

Plasma cell granuloma of the thyroid is an uncommon lesion; only 6 cases have been reported in the English literature to date. All reported cases occurred in women, mostly after the age of 50 years. We report a case of plasma cell granuloma of the thyroid in a 46-year-old woman with a 20-year history of euthyroid goiter and a positive family history of goiter in 3 close relatives. The lesion was composed of sheets of plasma cells involving the entire parenchyma that histologically resembled plasmacytoma. Plasmacytoma was excluded by demonstration of polyclonal κ/λ light chain immunostaining and by lack of evidence of clonal bands by polymerase chain reaction for immunoglobulin heavy-chain gene rearrangement. Similarly, the predominant histologic pattern in all previously reported cases is that of marked plasma cell infiltration. A family history of thyroid disease (goiter, thyroiditis) was associated with diffuse involvement of the thyroid. Prognosis after surgery is excellent, and to our knowledge no cases of malignant transformation or recurrence have been described.
Benign Fibrohistiocytoma (Xanthomatous Variant) of the Acromion
Authors: Macdonald Denis , Fornasier Victor , Holtby Richard
Published: January 2021

A number of fibrous lesions involving bone display almost identical histologic appearances yet may represent either reactive or neoplastic conditions, resulting in a confusing nomenclature and possible diagnostic confusion. We report the case of a young man with no significant previous medical history who presented with a painful lesion in the left shoulder, which consisted almost entirely of xanthomatous material. We discuss the possible differential diagnosis of this lesion and why benign fibrous histiocytoma is the preferred terminology for this lesion. To our knowledge, this is the first reported case of a benign fibrous histiocytoma involving the acromion in an adult.
Sarcomatoid Variant of Anaplastic Large Cell Lymphoma Mimicking a Primary Breast Cancer
Authors: Pereira Emílio M. , Maeda Sueli A. , Reis-Filho Jorge S.
Published: January 2021

The sarcomatoid variant of anaplastic large cell lymphoma is one of the rarest histologic variants of this neoplasm. Due to its sarcomatoid features, it is frequently misdiagnosed as a poorly differentiated sarcoma, anaplastic carcinoma, or melanoma. We report the case of a 92-year-old woman with a sarcomatoid anaplastic large cell lymphoma mimicking a primary breast neoplasm. The patient presented with a rapidly enlarging lump in the left breast and nodules in the right axilla. The immunohistochemical profile showed reactivity for leukocyte common antigen, UCHL-1, vimentin, and CD30, but immunoexpression of anaplastic lymphoma kinase was lacking. Anaplastic large cell lymphomas are lymphoid neoplasms of T-cell/null-cell lineage that consistently express the activation marker CD30 and usually carry a gene rearrangement of the anaplastic lymphoma kinase gene. To the best of our knowledge, this is the first reported case of sarcomatoid anaplastic large cell lymphoma presenting as a primary breast neoplasm in which anaplastic lymphoma kinase expression was assessed.
Myelolipoma Associated With Adrenal Ganglioneuroma
Authors: Merchant Shakil H. , Herman Christopher M. , Amin Mitual B. , Ro Jae Y. , Troncoso Patricia
Published: January 2021

Adrenal myelolipomas are rare, benign mesenchymal tumors composed of mature adipose tissue and hematopoietic cells in varying proportions. Although the majority of cases occur as isolated adrenal lesions, myelolipomas have been described in association with various adrenal pathologic conditions. These conditions include enzyme deficiencies and hyperplastic and neoplastic lesions of the adrenal cortex, with perhaps endocrine dysfunction as a common feature. Ganglioneuroma is a benign tumor of the sympathetic nervous system that rarely produces symptoms of endocrine dysfunction. We report an unusual case of myelolipoma associated with ganglioneuroma of the adrenal medulla. The histogenesis of myelolipoma remains speculative. However, the close proximity to adrenal cortical cells within the stroma of ganglioneuroma suggests that the hormonal microenvironment may have played a role in the development of the myelolipoma.
Epithelial Neoplasms of the Appendix and Colorectum
Authors: Carr Norman J. , Emory Theresa S. , Sobin Leslie H.
Published: January 2021

Context.—Carcinomas of the appendix are usually well-differentiated mucinous adenocarcinomas that tend to produce pseudomyxoma peritonei and do not show metastatic spread until late in the disease process. In contrast, adenocarcinomas of the colon and rectum rarely result in pseudomyxoma peritonei and frequently metastasize, even if mucinous and well differentiated. These differences in behavior may be reflected by differences at the molecular level.

Objectives.—To examine adenocarcinomas and their precursor lesions (adenomas) of the appendix and colorectum and to determine whether differences exist in the numbers of proliferating and apoptotic cells or in expression of p53, bcl-2, and the standard form of CD44 (CD44s).

Design.—Retrospective analysis of surgical specimens.

Setting.—Multicenter study.

Patients.—Individuals treated surgically for tumors of the appendix or colorectum.

Interventions.—Sections were cut from formalin-fixed surgical specimens and immunohistochemical tests were performed for Ki-67 (as a marker of proliferating cells), M30 (as a marker of apoptotic cells), p53, CD44s, and bcl-2.

Main Outcome Measures.—Expression of Ki-67, M30, p53, CD44s, and bcl-2 in tumor cells.

Results.—The appendiceal adenomas showed significantly lower Ki-67 counts, p53 expression, and bcl-2 expression. When compared with adenocarcinomas of the colorectum in general (mucinous and nonmucinous), the appendiceal adenocarcinomas showed significantly lower Ki-67 counts, M30 counts, and CD44s expression. However, when the analysis was confined to well-differentiated mucinous adenocarcinomas, only the M30 count was significantly different.

Conclusions.—The lower proliferative and apoptotic activity of appendiceal carcinomas and the lower CD44s expression are in keeping with their more indolent behavior compared with adenocarcinomas of the colorectum. However, when only the subset of well-differentiated mucinous adenocarcinomas was compared, only the apoptotic activity was different, suggesting that the other differences were related to the morphologic structure of the lesions.
Microcystic Transitional Cell Carcinoma
Authors: Leroy Xavier , Leteurtre Emmanuelle , De La Taille Alexandre , Augusto David , Biserte Jacques , Gosselin Bernard
Published: January 2021

Microcystic transitional cell carcinoma is a rare variant of urothelial carcinoma; to date, it has been described only in the urinary bladder. We report 2 cases of microcystic transitional cell carcinoma arising in the renal pelvis. The first case occurred in a 73-year-old man with a history of superficially invasive transitional cell carcinoma who presented with macroscopic hematuria and anemia. The second case occurred in a 62-year-old woman who had no relevant medical history and presented with hematuria. Computed tomographic scan revealed a tumor of the renal pelvis. In both cases, microscopic examination showed invasive transitional cell carcinoma with prominent cystic features. The cysts were irregular in size and were deeply infiltrative. The cysts were lined by single or multiple layers of cuboidal or flattened cells with minimal cytological atypia. The first patient died of his disease 18 months after presentation. The second patient remained well at her 6-month follow-up examination. Microcystic transitional cell carcinoma is an unusual, deceptively bland variant of urothelial carcinoma, which can mimic benign lesions.
Expression of Desmin and Smooth Muscle Myosin Heavy Chain in Dermatofibromas
Authors: Bruecks Andrea K. , Trotter Martin J.
Published: January 2021

Background.—The histopathologic features of dermatofibroma vary remarkably, and this diversity may occasionally cause problems in differentiating between benign and malignant mesenchymal lesions, including smooth muscle neoplasms. Immunohistochemical stains are sometimes necessary to clarify the histogenesis of a lesion.

Objective.—To evaluate dermatofibromas for expression of desmin and smooth muscle myosin heavy chain (SM-MHC) antigens, which are commonly used as evidence of smooth muscle differentiation.

Methods.—We studied 100 consecutive cases of dermatofibroma using hematoxylin-eosin–stained sections and immunoperoxidase staining with antibodies against desmin, SM-MHC, and smooth muscle actin.

Results.—We found focal positivity for desmin in 9 cases, and in 2 of these cases, at least 10% of lesional cells showed strong expression. We found focal staining for SM-MHC in 10 cases, and in 2 of these cases, at least 10% of the lesional cells were positive. Regions positive for desmin and/or SM-MHC did not show definite histologic features of myogenous differentiation on hematoxylin-eosin–stained sections. All dermatofibromas expressing desmin and SM-MHC were also strongly positive for smooth muscle actin.

Conclusions.—About 10% of dermatofibromas show focal expression of desmin and SM-MHC, and this expression may be present in up to 10% to 15% of lesional cells. Thus, in dermal spindle cell lesions, focal expression of these muscle antigens, like that of smooth muscle actin, is not diagnostic of a smooth muscle tumor.
Detection of Factor V Leiden and Prothrombin Gene Mutations in Patients Who Died With Thrombotic Events
Authors: Ranguelov Rostislav D. , Rosenthal Nancy , Bromley Christine , Vasef Mohammad A.
Published: January 2021

Context.—Individuals with factor V or prothrombin gene mutations are at increased risk for thrombotic events. Furthermore, the risk of recurrent deep venous thrombosis in heterozygous carriers of both factor V Leiden and prothrombin gene mutations is high enough that some investigators suggest lifelong warfarin prophylaxis for these individuals, even with a single spontaneous thrombotic event.

Objectives.—To assess the incidence of factor V Leiden and prothrombin gene mutations in an autopsy population and to determine if these tests can prove useful in identification of at-risk family members.

Design.—We analyzed factor V Leiden and prothrombin gene mutations in 45 patients who died with or of thrombotic events, using archival tissue and multiplex allele-specific polymerase chain reaction amplification. The wild-type factor V gene was amplified in all 45 patients, whereas the wild-type prothrombin gene was amplified in 29 patients.

Results.—Two patients (4.4%) who died with thrombotic events at the ages of 35 and 92 years were heterozygous for factor V gene mutation. Two additional patients (6.7%), who died with thrombotic events at the ages of 26 and 39 years, were heterozygous for prothrombin gene mutation. Patients homozygous for either factor V or prothrombin gene or simultaneously heterozygous for both genes were not detected in our study.

Conclusions.—Our findings suggest that screening the relatives of elderly patients who die with thrombotic events would not be cost-effective because of the low incidence of these mutations in the autopsy population. However, because the incidence of these mutations appeared significantly more frequently among individuals who died at 39 years or younger, testing the relatives of this subset of patients may prove useful for detection of at-risk individuals who would benefit from preventive anticoagulation therapy.
Nonseminomatous Germ Cell Tumor Arising in Splenogonadal Fusion
Authors: Imperial Sandy L. , Sidhu Jagmohan S.
Published: January 2021

Splenogonadal fusion is a rare congenital malformation in which the spleen is abnormally connected to the gonads or to the mesonephric derivatives. A few more than 150 cases have been described in the world literature. We report an additional case of splenogonadal fusion. A nonseminomatous germ cell tumor was found in the testicle involved in this splenogonadal fusion. To our knowledge, this is the third reported case of a testicular neoplasm associated with splenogonadal fusion and the first reported case of intra-abdominal nonseminomatous germ cell testicular tumor arising in this rare anomaly. The literature pertaining to splenogonadal fusion and the testicular tumor arising in this anomaly is briefly reviewed.
Plasminogen and Tissue-Type Plasminogen Activator Deficiency as Risk Factors for Thromboembolic Disease
Authors: Brandt John T.
Published: January 2021

Objective.—To review the published evidence for an association between a deficiency of plasminogen or tissue-type plasminogen activator (tPA) and the risk of thrombosis.

Data Sources.—Review of the medical literature, with an emphasis on the last 10 years.

Data Extraction and Synthesis.—After an initial assessment of the literature, including review of clinical study design and laboratory methods, a draft manuscript summarizing the findings was prepared and circulated to participants in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia. The key findings and each recommendation were presented for discussion at the conference. Recommendations were accepted if a consensus of the 27 experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form.

Conclusions.—The consensus of the conference was that routine laboratory assessment of plasminogen and tPA concentration in patients with thrombophilia is not warranted at this time. Analysis of plasminogen and tPA gene alterations in patients with thrombophilia is also not warranted at this time. Determination of plasminogen concentration should be performed in patients suspected of having ligneous conjunctivitis.