bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Morphogenetic Proteins Are Expressed by Both Bone-Forming and Non–Bone-Forming Lesions
Authors: Khurana Jasvir S. , Ogino Shuji , Shen Ting , Parekh Hemant , Scherbel Uwe , DeLong William , Feldman Michael D. , Zhang Paul J. , Wolfe Hubert J. , Alman Benjamin A.
Published: February 2021

Context.—Bone morphogenetic proteins (BMPs) are thought to be responsible for bone formation; they cause bone to form in soft tissues and are clinically used in helping fracture union or tumor reconstructions. Skeletal metastases from epithelial tumors may be either bone-forming (blastic) or non–bone-forming (lytic).

Objective.—We studied the expression of BMPs in a variety of primary and secondary lesions of bone (both bone-forming and non–bone-forming) to determine if there was a consistent relationship between bone formation and BMP expression.

Design.—We compared a bone-forming lesion (fibrous dysplasia) with a non–bone-forming lesion (desmoid tumor), using reverse transcription–polymerase chain reaction, Northern blot analysis, and immunohistochemistry to detect BMPs. We also studied a number of non–bone-forming secondary lesions (carcinomas that formed lytic metastases to the skeleton) and found BMP production in most of these tumors.

Results.—We found that BMPs were expressed in both bone-forming and non–bone-forming benign musculoskeletal lesions. In the first part of the study, BMPs were found in both fibrous dysplasia and desmoid tumors. Bone morphogenetic proteins were also expressed by several tumors. In the next part of the study (paraffin-embedded tissue), BMPs were expressed by a variety of tumors, irrespective of the radiological nature (blastic or lytic) of their metastases.

Conclusions.—We conclude that BMP production alone cannot explain bone formation, and other factors either alone or in combination may be responsible for blastic metastases to the skeleton and for bone formation by primary bone lesions, such as fibrous dysplasia.
Soft Tissue Amyloidoma of the Extremities: A Case Report and Review of the Literature
Authors: Bardin Richard L. , Barnes Craig E. , Stanton Constance A. , Geisinger Kim R.
Published: February 2021

The deposition of amyloid as a distinct, clinically apparent mass is uncommon, particularly in soft tissues. Among reported sites of soft tissue amyloidomas, the extremities are quite rare. Amyloid tumors can mimic malignant neoplasms both clinically and radiologically. We report a case of AA amyloidoma presenting in the deltoid region with radiological features suggesting sarcoma. Cytomorphology from fine-needle aspiration material, tissue histology, and appearance by magnetic resonance imaging are described. The literature on soft tissue amyloidoma is reviewed.
Diffuse Giant Inflammatory Polyposis: A Challenging Clinicopathologic Diagnosis
Authors: Sheikholeslami Mohammad-Reza , Schaefer Robert F. , Mukunyadzi Perkins
Published: February 2021

Giant inflammatory polyposis of the colon is an uncommon manifestation of inflammatory bowel disease. We report a unique case of localized diffuse giant inflammatory polyposis in a 58-year-old white man, which was characterized by recurrence following initial surgical resection. The patient presented with symptoms of abdominal pain and passing blood per rectum. Colonoscopic examination revealed a near-obstructing, “fungating” mass in the sigmoid colon, which clinically was thought to represent colon carcinoma. Histology of several colon biopsies revealed marked acute inflammation with microabscess formation of the polyps and the adjacent mucosa. There was no evidence of dysplasia or malignancy. Because malignancy was strongly suspected and to relieve the obstructive symptoms, the patient underwent a segmental colectomy. The histologic features of the resected mass showed giant polyps with acute inflammation diagnostic of giant inflammatory polyposis. Again, there was no evidence of malignancy. Seven months later, following an uneventful initial postoperative recovery, the patient developed a recurrence of the mass with obstructive symptoms and required further surgical resection. The gross and histologic features of the lesion were similar to the previous findings. This case highlights the varied presenting symptoms and deceptive gross colonoscopic and radiologic features of localized diffuse giant inflammatory polyposis. Finally, the presence of inflammation at the resection margins appears to predict recurrence or persistence of the disease.
Severe Acute Respiratory Syndrome: Overview With an Emphasis on the Toronto Experience
Authors: Mazzulli Tony , Kain Kevin , Butany Jagdish
Published: February 2021

Objective.—To provide an overview of the severe acute respiratory syndrome (SARS) outbreak in Toronto, Ontario, which experienced the largest outbreak outside Asia, and to review what has been learned during the past year.

Data Sources.—MEDLINE search of all studies related to SARS, including review of the Centers for Disease Control and Prevention, World Health Organization (WHO), and Health Canada Web sites.

Data Synthesis.—During the SARS outbreak in Toronto, 438 people had been diagnosed as having suspected or probable SARS and 44 people died. Elderly people and those with comorbid illnesses were at greatest risk of complications or death. Transmission was via direct contact with respiratory secretions. The use of gloves, gowns, N95 masks, and eye protection was effective in preventing transmission. No transmission occurred before symptom onset or after recovery. Serologic tests suggest that antibodies may not appear until 28 days after illness onset. Molecular tests give their greatest yield during the second week of illness. The value of ribavirin treatment remains questionable. The combination of interferon plus corticosteroids appears to be better than corticosteroids alone. Postmortem examination revealed pulmonary edema and evidence of diffuse alveolar damage. Very few morphological changes were noted in other organs despite the presence of viral RNA as detected by polymerase chain reaction.

Conclusion.—On July 5, 2003, the WHO declared that the SARS outbreak was over. Since then, new cases of SARS have been reported in Asia. With global travel, the disease can rapidly spread throughout the world. Therefore, we must remain vigilant to prevent another pandemic.
Pulmonary and Ophthalmic Involvement With Erdheim-Chester Disease: A Case Report and Review of the Literature
Authors: Allen Timothy Craig , Chevez-Barrios Patricia , Shetlar Debra J. , Cagle Philip T.
Published: February 2021

Erdheim-Chester disease is a rare nonfamilial histiocytic disorder of unknown etiology with characteristic long bone findings. The 3-year survival rate for patients with Erdheim-Chester disease is 50%. Approximately 50% of patients have disease involvement in other tissues, including skin, retro-orbital and periorbital tissues, pituitary-hypothalamic axis, heart, kidney, retroperitoneum, breast, skeletal muscle, and sinonasal mucosa; about 20% of patients have lung involvement. Prognosis generally depends on the extent of the extraosseous disease. For patients with lung involvement, gender distribution is equal, but men typically present at an older age than do women. Approximately 80% of patients present with dyspnea, and most patients have diffuse interstitial infiltrates and pleural and/or interlobar septal thickening on chest radiology. Characteristic lung histopathology includes the accumulation of histiocytes with variable amounts of fibrosis and a variable lymphoplasmacytic infiltrate in a lymphangitic distribution. Immunostains are diagnostically useful, showing immunopositivity for CD68 and factor XIIIa and immunonegativity for CD1a. Birbeck granules are uniformly absent ultrastructurally.
Comparison of Performance of Conventional and ThinPrep Gynecologic Preparations in the College of American Pathologists Gynecologic Cytology Program
Authors: Renshaw Andrew A. , Young Nancy A. , Birdsong George G. , Styer Patricia E. , Davey Diane D. , Mody Dina R. , Colgan Terence J.
Published: February 2021

Context.—Results of clinical trials suggest that interpretation of liquid-based cytology preparations is more accurate and is associated with less screening error than interpretation of conventional preparations.

Objective.—In this study, the performance of participants in interpreting ThinPrep (TP) preparations was compared with participants' performance on conventional Papanicolaou tests in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP).

Design.—The results of the PAP from the year 2002 were reviewed, and the discordancies to series and exact-match error rates for the 2 cytologic methods were compared.

Results.—For this study, a total of 89 815 interpretations from conventional smears and 20 886 interpretations from TP samples were analyzed. Overall, interpretations of TP preparations had both significantly fewer false-positive (1.6%) and false-negative (1.3%) rates than those of conventional smears (P = .001 and P = .02, respectively) for validated or validated-equivalent slides, as assessed by concordance with the correct diagnostic series. In this assessment of concordance to series, interpretations of educational TP and conventional preparations were similar, except for high-grade squamous intraepithelial lesion, in which the performance was significantly worse for educational TP preparations (false-negative rate of 8.1% vs 4.1% for conventional smears, P < .001). When interpretations were matched to the exact diagnosis, validated-equivalent TP preparations were generally more accurate for diagnoses in the 100 series and 200 series than were conventional smears. Notably, for the reference diagnosis of squamous cell carcinoma, the exact-match error rate on validated equivalent TP slides was significantly greater than that of conventional slides (44.5% vs 23.1%, P < .001). Interpretations of educational TP preparations also had a significantly higher error rate in matching to the exact reference diagnosis for squamous cell carcinoma (33.7% vs 22.8%, P = .007).

Conclusions.—Overall, TP preparations in this program were associated with significantly lower error rates than conventional smears for both validated and educational cases. However, unlike the negative for intraepithelial lesion and malignancy, not otherwise specified, low-grade squamous intraepithelial lesion, and adenocarcinoma cytodiagnostic challenges, participants' responses indicated some difficulty in recognizing high-grade squamous intraepithelial lesion and squamous cell carcinoma.
Jejunal Gastrointestinal Stromal Tumor: A Cause of Obscure Gastrointestinal Bleeding
Authors: Sass David A. , Chopra Kapil B. , Finkelstein Sydney D. , Schauer Philip R.
Published: February 2021

In cases of obscure gastrointestinal bleeding, when a source for blood loss is not apparent from examination of the colon and upper gastrointestinal tract, the small bowel usually becomes the focus of investigation. A tumor with interesting pathologic features was found in a patient who presented with recurrent episodes of massive obscure gastrointestinal hemorrhage. This case highlights the importance of considering small intestinal tumors as the likely cause of obscure gastrointestinal hemorrhage in young patients and how a noninvasive test, eg, abdominal computed tomography scan, might obviate the need for more invasive testing.
Primary Small Bowel Carcinoid Tumor With Bilateral Breast Metastases: Report of 2 Cases With Different Clinical Presentations
Authors: Mosunjac Marina B. , Kochhar Ruby , Mosunjac Mario I. , Lau Stephen K.
Published: February 2021

Context.—Carcinoid tumor metastatic to the breast is uncommon and can closely mimic a mammary carcinoma. The differentiation of metastatic carcinoid tumor from primary breast tumor is important, however, owing to different clinical management and prognosis.

Objective.—The purpose of this study was to describe 2 patients with bilateral metastatic carcinoid tumors to the breast with different clinical manifestations.

Design.—We examined the radiological, clinical, cytologic, histologic, immunohistochemical, and ultrastructural features of these 2 cases.

Results.—In case 1, the tumor presented initially as a stellate mass on mammogram and was diagnosed as grade II infiltrating ductal carcinoma. It was only after the discovery of small intestinal, liver, ovarian, and contralateral breast masses, as well as careful morphologic and immunohistochemical evaluations, that the true nature of the tumor was realized. In case 2, the tumor initially presented as a small intestinal tumor with liver metastases and bilateral breast masses. The breast masses were diagnosed accurately as metastatic carcinoid tumor by morphologic and immunohistochemical evaluations.

Conclusions.—Metastatic carcinoid tumor to the breast is uncommon, but poses a diagnostic challenge in that morphologically it can closely mimic a primary breast tumor. Careful attention to clinical features and the use of auxiliary immunohistochemical studies can help in arriving at the correct diagnosis.
In-house Calibration of the International Sensitivity Index or Calibration Curve for Determination of the International Normalized Ratio
Authors: Brien William F. , Crawford Linda , Raby Anne , Richardson Harold
Published: February 2021

Context.—The international normalized ratio (INR) has been used since 1983 to standardize prothrombin time results for patients on oral anticoagulants. However, significant interlaboratory variations have been noted. Attempts have been made to address these differences with the use of instrument-specific International Sensitivity Index (ISI) values and in-house calibration of ISI values.

Objective.—To assess the performance of laboratories using a calibration curve for INR testing.

Design.—Attempts to improve performance of the INR include the use of instrument-specific ISI values, model-specific ISI values, in-house calibration of ISI values, and more recently, the preparation of a calibration curve. Several studies have shown an improvement in performance using these procedures. In this study of licensed laboratories performing routine coagulation testing in the Province of Ontario, Canada, the determination of the INR by a calibration curve was compared with the laboratories' usual method of assessment. These methods were subsequently analyzed by comparing the results to instrument-specific ISI, model-specific ISI, and in-house calibrators. International normalized ratios derived by both methods were analyzed for accuracy and precision. The stability of a calibration curve was also investigated.

Results.—Performance of INR testing has improved with use of a calibration curve or in-house calibrators.

Conclusion.—The results confirm that either in-house calibrators or the calibration curve improve performance of INR testing. The calibration curve may be easier to use and appears stable up to 4 months.
Testicular Extramedullary Myeloid Cell Tumor: Report of a Case With Unique Clinicopathologic Features and a Brief Review of the Literature
Authors: Rawal Ajay , Keeler Thomas C. , Milano Michelangelo A.
Published: February 2021

We report a case of testicular extramedullary myeloid cell tumor in a 37-year-old man who presented with an acute testicular hemorrhage. A pathologic examination revealed no gross tumor mass. A well-differentiated extramedullary myeloid cell tumor infiltrate was seen histologically, localized largely to the seminiferous tubules. The patient had no evidence of any past or concurrent myeloid disorders. The lack of the usual clinical features of a testicular mass and the presence of an intratubular pattern of infiltration can further compound the challenges in diagnosing this entity.
Pathology Abbreviated: A Long Review of Short Terms
Authors: Berman Jules J.
Published: February 2021

Context.—Abbreviations are used frequently in pathology reports and medical records. Efforts to identify and organize free-text concepts must correctly interpret medical abbreviations. During the past decade, the author has collected more than 12 000 medical abbreviations, concentrating on terms used or interpreted by pathologists.

Objective.—The purpose of the study is to provide readers with a listing of abbreviations. The listing of abbreviations is reviewed for the purpose of determining the variety of ways that long forms are shortened.

Design.—Abbreviations fell into different classes. These classes seemed amenable to distinct algorithmic approaches to their correct expansions. A discussion of these abbreviation classes was included to assist informaticians who are searching for ways to write software that expands abbreviations found in medical text. Classes were separated by the algorithmic approaches that could be used to map abbreviations to their correct expansions. A Perl implementation was developed to automatically match expansions with Unified Medical Language System concepts.

Measurements.—The abbreviation list contained 12 097 terms; 5772 abbreviations had unique expansions. There were 6325 polysemous abbreviation/expansion pairs. The expansions of 8599 abbreviations mapped to Unified Medical Language System concepts. Three hundred twenty-four abbreviations could be confused with unabbreviated words. Two hundred thirteen abbreviations had different expansions depending on whether the American or the British spellings were used. Nine hundred seventy abbreviations ended in the letter “s.”

Results.—There were 6 nonexclusive groups of abbreviations classed by expansion algorithm, as follows: (1) ephemeral; (2) hyponymous; (3) monosemous; (4) polysemous; (5) masqueraders of common words; and (6) fatal (abbreviations whose incorrect expansions could easily result in clinical errors).

Conclusion.—Collecting and classifying abbreviations creates a logical approach to the development of class-specific algorithms designed to expand abbreviations. A large listing of medical abbreviations is placed into the public domain. The most current version is available at http://www.pathologyinformatics.org/downloads/abbtwo.htm.
Comparison of Human Papillomavirus DNA Prevalence in Atypical Squamous Cells of Undetermined Significance Subcategories as Defined by the Original Bethesda 1991 and the New Bethesda 2001 Systems
Authors: Pirog Edyta C. , Erroll Maria , Harigopal Malini , Centeno Barbara A.
Published: February 2021

Context.—The new Bethesda System 2001 (TBS 2001) minimized the subclassification of atypical squamous cells of undetermined significance (ASCUS).

Objective.—The primary goal of this study was to determine the impact of the new subclassification on the accuracy of Papanicolaou (Pap) test diagnosis by examining the prevalence of human papillomavirus (HPV) DNA in different ASCUS subcategories, as defined by the new TBS 2001 versus the original TBS 1991. The second goal was to identify specific morphologic features of atypical squamous cells that are more frequently associated with HPV detection.

Design.—Consecutive cases of ThinPrep Pap tests were retrospectively reviewed by a panel of pathologists to obtain consensus diagnoses. The study group consisted of ASCUS cases; the positive control group consisted of low- and high-grade squamous intraepithelial lesions (LSILs and HSILs, respectively); and the negative control group consisted of cases “negative for intraepithelial lesion or malignancy.” All ASCUS cases were subclassified according to TBS 1991 into the following categories: favor reactive (ASCUS-R), favor LSIL (ASCUS-L), favor HSIL (ASCUS-H), and not otherwise specified (ASCUS-NOS). In a separate review, ASCUS cases were subclassified according to TBS 2001 into the following categories: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). Furthermore, morphologic ASCUS subtypes were recorded (atypical mature, immature, parakeratotic, and atrophic cells); in addition, individual morphologic features of atypical cells were recorded. Broad- spectrum HPV DNA amplification and genotyping was performed using short PCR fragment (SPF 10) polymerase chain reaction/Line Probe assays.

Results.—In cases classified according to TBS 1991, HPV was detected in 32% of negative, 49% of ASCUS, and 93% of LSIL/HSIL cases. On the second review, using the diagnostic categories of TBS 2001, which eliminated the ASCUS-;R category, the number of ASCUS cases decreased by 45%. The prevalence of HPV DNA in ASCUS cases downgraded to the negative category was 38%, which was not significantly different from HPV prevalence in negative cases as diagnosed under TBS 1991. Furthermore, HPV was detected in 56% of ASC-US and 71% of ASC-H cases. The prevalence of HPV in different morphologic subtypes of ASCUS was not significantly different, and none of the 8 individual morphologic features of atypical cells were more frequently associated with HPV detection.

Conclusion.—Elimination of the ASCUS-R category in TBS 2001 resulted in a significant decrease in the number of ASCUS diagnoses. Downgraded cases had a relatively low prevalence of HPV DNA. It is expected that TBS 2001 will increase specificity of the Pap test without compromising its sensitivity.
Early Stage of Epstein-Barr Virus Lytic Infection Leading to the “Starry Sky” Pattern Formation in Endemic Burkitt Lymphoma
Authors: Fujita Shuichi , Buziba Nathan , Kumatori Atsushi , Senba Masachika , Yamaguchi Akira , Toriyama Kan
Published: February 2021

Context.—Burkitt lymphoma (BL) is histologically characterized by a “starry sky” appearance, representing scattered macrophages that have phagocytosed cell debris among proliferating lymphoma cells. As is well known, almost all the neoplastic cells of endemic BL are infected with Epstein-Barr virus (EBV). Previous studies have indicated that most of the EBV in B cells is latent, and few virus particles enter the lytic cycle.

Objective.—To examine the histologic relationship between EBV infection stages and the formation of the starry sky pattern in African endemic BL tissues.

Design.—Tissue samples from 44 patients with African endemic BL were examined with immunohistochemistry and in situ hybridization. We used EBV-encoded small RNA (EBER) as a marker of latent infection, and BamHI H left frame 1 (BHLF1) and BamHI Z EBV replication activator (ZEBRA) as lytic cycle markers.

Results.—In all cases, signals for EBER were found in most neoplastic lymphocytes, and in 73% of cases, signals for BHLF1 and/or ZEBRA were recognized in the lymphoma cells within and around the lacunae in starry sky figures. The mean number of lacunae per unit area in cases positive for lytic cycle markers was significantly higher than that in negative cases (P < .001).

Conclusions.—Our findings suggest that EBV-infected lymphoma cells in the lytic cycle, which eventually lapse into cell death, are phagocytosed prior to their rupture by macrophages that have migrated into the parenchyma. We emphasize that transition of EBV-infected lymphoma cells to the lytic cycle is one of the histomorphogenetic factors influencing the formation of starry sky pattern in endemic BL.
Gastric Myeloid Metaplasia: A Case Report and Review of the Literature
Authors: Chatelain Denis , Devendeville Agnès , Rudelli Alain , Bruniau Alexis , Geslin Guillaume , Sevestre Henri
Published: February 2021

We report a case of gastric myeloid metaplasia in an 89- year-old woman with agnogenic myeloid metaplasia. The lesions were fortuitously discovered on upper endoscopy. The antral mucosa was thickened and polypoid, and on histologic examination contained immature granulocytes, megakaryocytes, and a few erythroblasts without desmoplastic stromal reaction. The granulocytes were positive for CD15, CD68, and myeloperoxidase on immunohistochemistry, and the megakaryocytes showed positive reactivity for factor VIII. Gastric myeloid metaplasia is a very rare event, and to our knowledge only 6 cases have been reported in the literature to date. It usually occurs in patients with advanced myeloproliferative syndrome. Gastric myeloid metaplasia often has a pseudotumoral appearance, leading to digestive symptoms. Histologic diagnosis is straightforward when trilinear hematopoietic elements are identified in gastric biopsies. Immunohistochemistry with anti–factor VIII antibody can be useful to confirm the presence of megakaryocytes.
Primitive Neuroectodermal Tumor of the Gallbladder
Authors: Song Dong Eun , Choi Ga Won , Jun Sun-Young , Ro Jae Y.
Published: February 2021

Ewing sarcoma/primitive neuroectodermal tumor (ES/ PNET) most commonly occurs in the soft tissues of the extremities and the paravertebral areas. To our knowledge, no case of PNET has been reported in the gallbladder to date. We report a case of PNET of the gallbladder occurring in a 53-year-old woman. Microscopically, the monotonous small round cells with a formation of Homer-Wright rosettes showed intense membranous positive immunoreactivity for MIC2/CD99, as well as for neuron-specific enolase and synaptophysin. Other small round cell tumors, such as lymphoma, rhabdomyosarcoma, or melanoma, were excluded in light of negative immunoreactivity for leukocyte common antigen, desmin, and S100. The diagnosis of PNET was rendered based on the characteristic morphology and immunohistochemical findings, despite an absence of chromosomal translocations, such as t(11; 22)(q24;q12) and t(21;22)(q22;q12).
Comparison of Needle Core Biopsy and Fine-Needle Aspiration for Diagnostic Accuracy in Musculoskeletal Lesions
Authors: Yang Yi Jun , Damron Timothy A.
Published: February 2021

Context.—Needle core biopsy has been reported to be the choice of biopsy for musculoskeletal tumors. Fine-needle aspiration, on the other hand, has been widely accepted for nonmusculoskeletal tumors, but is only used in selected medical centers for musculoskeletal tumors. While fine-needle aspiration appears to have advantages to needle core biopsy in the aspects of simplicity and cost, the diagnostic accuracy should be the most critical parameter in determining the choice of biopsy. However, few studies comparing the diagnostic accuracy of these 2 biopsy methods have been performed.

Objective.—This study was designed to compare the diagnostic accuracy of fine-needle aspiration and needle core biopsy in musculoskeletal tumors.

Design.—Prospective study was performed in patients aged 10 years or older. Diagnostic accuracy was compared in 50 consecutive concurrent needle core biopsies and fine-needle aspirations of musculoskeletal lesions.

Results.—For primary musculoskeletal lesions, fine-needle aspiration achieved a diagnostic accuracy rate of 88% for nature of lesion, 64% for specific diagnosis, 78% for histologic grading, and 74% for histologic typing. Needle core biopsy achieved an accuracy rate of 93% for nature of lesions, 83% for specific diagnosis, 83% for histologic grading, and 90% for histologic typing. Both biopsy methods have a higher diagnostic accuracy rate for high-grade tumors than for low-grade or benign lesions in determining the nature, specific diagnosis, and histologic grading.

Conclusions.—The needle core biopsy has a higher diagnostic accuracy than fine-needle aspiration in all aspects, including determining the nature of the tumor, establishing the histologic type and grade, and achieving a specific diagnosis.
Quality Control Analysis of the Potential for Asbestos Contamination During Tissue Processing inPathology Laboratories
Authors: Dodson Ronald F. , O'Sullivan Michael , Hammar Samuel P.
Published: February 2021

Context.—Various quality assurance procedures are applied in pathology and analytical microscopy laboratories to ensure accurate results.

Objective.—To assess the potential of cross-contamination of tissue with asbestos fibers and asbestos bodies during the fixation and washing process.

Design.—Lung tissue from 10 patients with potential asbestos-related disease was evaluated. Samples of fixative, water, and lung tissue from each case were evaluated by light and analytical transmission electron microscopy for asbestos bodies and uncoated asbestos fibers.

Results.—The lung samples tested contained a range of asbestos bodies and uncoated asbestos fibers. One wash water sample contained one asbestos body. No asbestos bodies or uncoated asbestos fibers were found in any other water or fixative samples.

Conclusions.—The absence of uncoated asbestos fibers in wash water or fixative samples argues that the fixation process stabilizes asbestos fibers within tissue and the protocol used in this pathology laboratory protects against cross-contamination of tissue. The finding of one asbestos body in one water sample further supports the efficiency of the protective controls used in the testing methods, since this asbestos body was in the external solution that was being discarded before tissue sampling occurred.
Massive Thyroid Tumoral Embolism From a Breast Carcinoma Presenting as Acute Thyroiditis
Authors: Jiménez-Heffernan Jose A. , Perez Francisco , Hornedo Javier , Perna Cristian , Lapuente Fernando
Published: February 2021

We describe an unusual case of metastatic disease to the thyroid, characterized by massive intra-arterial embolization and clinical presentation as acute thyroiditis. The patient, a 37-year-old woman with a history of breast carcinoma, presented clinically with acute thyroiditis. No nodules were palpable, and fine-needle aspiration cytology of the left lobe was performed. It showed a pleomorphic carcinoma and was followed by total thyroidectomy. Histology disclosed a pleomorphic carcinoma diffusely affecting the thyroid gland. It was characterized by an extensive intra-arterial tumoral embolization. Immunohistochemistry confirmed the metastatic nature of the neoplasm. This is a very uncommon form of metastatic disease to the thyroid. The ischemia and necrosis associated with the embolic process were most probably responsible for this clinical presentation. This atypical clinical and cytologic presentation may induce confusion with a primary neoplasm, mainly anaplastic thyroid carcinoma.
Amiodarone-Induced Thyrotoxicosis and Thyroid Cancer: Clinical, Immunohistochemical, and Molecular Genetic Studies of a Case and Review of the Literature
Authors: Saad Aly , Falciglia Mercedes , Steward David L. , Nikiforov Yuri E.
Published: February 2021

Amiodarone-induced thyrotoxicosis (AIT) is a well-known complication of amiodarone treatment found in 3% to 12% of patients. Two types of AIT have been described, each associated with a distinct histologic pattern of thyroid involvement. Type 1, which typically develops in the background of pre-existing thyroid disease, is due to iodine-induced excess thyroid hormone synthesis, whereas type 2 is due to destructive thyroiditis. The prevalence of thyroid cancer in patients with AIT is unknown. We report a case of papillary thyroid carcinoma associated with type 2 AIT.
Spindle Cell Transformation of Papillary Carcinoma
Authors: Brandwein-Gensler Margaret S. , Wang Beverly Y. , Urken Mark L.
Published: February 2021

Spindle cells are not routinely encountered in the context of thyroid pathology and are most often present in anaplastic thyroid carcinoma, medullary thyroid carcinoma, and benign conditions such as Riedel struma or de Quervain granulomatous thyroiditis. Only a few publications have reported papillary thyroid carcinoma admixed with a prominent spindle cell component. While these tumors are clearly distinct from anaplastic thyroid carcinoma, prognostication as to their oncologic potential is not yet established. We describe a unique case of spindle cell transformation of papillary thyroid carcinoma. The blandness of the spindle cells was so impressive as to dissuade us from a malignant diagnosis on preoperative biopsies. However, this patient unfortunately died shortly after transformation of this papillary thyroid carcinoma. We conclude that this peculiar and rare spindle cell transformation should be regarded as a potentially lethal variant of papillary thyroid carcinoma.
A Unique Collision Tumor in Breast
Authors: Susnik Barbara , Jordi Rowe J. , Redlich Philip N. , Chitambar Christopher , Chang Chung-Che , Kampalath Bal
Published: February 2021

We report an extraordinary case of a collision tumor consisting of invasive ductal carcinoma with adjacent malignant lymphoma presenting as a single mass in the breast. A 79-year-old woman presented with a breast mass. A core biopsy performed at an outside hospital was interpreted as medullary carcinoma. On review of the breast core biopsy, a diagnosis of a synchronous malignant lymphoma and invasive ductal carcinoma was rendered. The patient underwent lumpectomy and axillary dissection. The excised specimen revealed a 2.1-cm, moderately differentiated invasive ductal carcinoma, partially surrounded by malignant lymphoma with areas where both tumors were intermixed. All 27 axillary lymph nodes were extensively involved by lymphoma, and 1 lymph node demonstrated metastatic carcinoma. The morphology and results of immunohistochemistry, flow cytometry, and cytogenetic analysis were consistent with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.
Oncocytic Biliary Cystadenocarcinoma: A Case Report and Review of the Literature
Authors: Bardin Richard L. , Trupiano Jacqueline K. , Howerton Russell M. , Geisinger Kim R.
Published: February 2021

We report an unusual case of biliary cystadenocarcinoma with oncocytic differentiation. The patient was a 43-year-old woman who presented with right upper quadrant pain. Imaging revealed a 16 × 10 × 10-cm, heterogenous, right hepatic mass with extension into the right atrium. Surgical resection revealed a papillary neoplasm of malignant cells with atypical hyperchromatic nuclei and prominent nucleoli lining fibrovascular cores. Mesenchymal stroma was not present. The majority of the epithelial cells had abundant eosinophilic granular cytoplasm, consistent with oncocytic differentiation. There was extensive stromal and hepatic parenchymal invasion. Immunohistochemical staining revealed a “biliary pattern” of cytokeratin subset immunoreactivity, with positivity for cytokeratin 7 and an absence of staining with cytokeratin 20. The tumor was negative for mucin, carcinoembryonic antigen, α-fetoprotein, calretinin, CD31, and chromogranin. There was granular cytoplasmic staining with phosphotungstic acid hematoxylin, consistent with the presence of abundant mitochondria. Electron microscopy revealed abundant mitochondria within the neoplastic cells. This case is quite unusual because female patients only rarely lack the characteristic ovarian-like mesenchymal stroma of biliary cystadenomas/cystadenocarcinomas. Furthermore, to our knowledge, oncocytic differentiation in this neoplasm has been reported previously on only 2 occasions. The biologic behavior and prognostic significance, if any, of the lack of mesenchymal stroma in female patients or the presence of oncocytic differentiation remains to be further elucidated as more of these cases are described.
College of American Pathologists Special Topic Symposium on Error in Pathology and Laboratory Medicine—Practical Lessons for the Pathologist: Introduction
Authors: Zarbo Richard J. , Sirota Ronald L.
Published: February 2021

This article is an overview to the all-day special topic symposium on patient safety and error reduction, entitled “Error in Pathology and Laboratory Medicine: Practical Lessons for the Pathologist,” which was held at the College of American Pathologists annual meeting in Scottsdale, Ariz, on September 20, 2004. The intent of the symposium was to provide pathologists with useful take-home lessons related to error identification, reduction, and risk avoidance for adoption in practice. Error reduction in the laboratory has always been an implied, if not directly stated goal of laboratory quality management programs, but given the nature of humans to err, the call for redesign of the health care system, and the impending threat of national patient safety legislation calling for medical error reporting and disclosure, we believe that this topic of error will be one of continued interest to practicing pathologists for many years.
Immunohistochemical and Clinicopathologic Characteristics of Invasive Ductal Carcinoma of Breast With Micropapillary Carcinoma Component
Authors: Kim Mi-Jung , Gong Gyungyub , Joo Hee Jae , Ahn Se-Hyun , Ro Jae Y.
Published: February 2021

Context.—A micropapillary carcinoma (MC) component is generally considered to behave aggressively. Although several reports have described the prognostic significance of MC in breast carcinomas, immunohistochemical findings of MC, especially as compared to non-MC, are rarely described.

Objective.—We compared clinicopathologic and immunohistochemical findings between 38 cases of invasive breast carcinoma with an MC component (IMC) and 217 cases of invasive breast carcinoma without an MC component (NIMC).

Design.—We constructed a tissue microarray from 38 cases of IMC and performed immunohistochemical stainings for cytokeratin (CK) 7, CK20, estrogen receptor, progesterone receptor, p53, c-Erb-B2, CD34, CK5, epidermal growth factor receptor, and c-Kit in both MC and non-MC components.

Results.—Cases with IMC were associated with greater tumor size, more frequent lymphovascular invasion, nodal metastases, greater mean numbers of positive lymph nodes, and higher stage than those with NIMC, but were not associated with poorer survival rates. On immunohistochemistry, only p53 reactivity was statistically different between MC and non-MC components in IMC cases. Estrogen receptor positivity tended to be lower in MC than non-MC, but the difference was not significant. Most of the MCs and non-MCs in IMC cases were positive for CK7, but none of them were positive for CK20, CK5, epidermal growth factor receptor, or c-Kit.

Conclusions.—Based on the frequent nodal metastases and association with higher stage found in IMC as compared with NIMC cases, as well as higher p53 positivity and lower frequency of estrogen receptor expression, MC could be considered an aggressive histologic type of breast carcinoma. In both MC and non-MC components in IMC cases, no basallike immunostaining pattern was detected.
Myelodysplastic Syndromes: Clinicopathologic Features, Pathobiology, and Molecular Pathogenesis
Authors: Nishino Ha Thanh , Chang Chung-Che
Published: February 2021

Context.—Myelodysplastic syndromes (MDSs) are clonal stem cell diseases characterized by ineffective hematopoiesis, multilineage dysplasia, and peripheral cytopenias with normocellular or hypercellular marrow. They represent a heterogeneous group of disorders with a varied spectrum of clinical, morphologic, biologic, and genetic characteristics. This heterogeneity in disease characterization has led to evolving classification systems, developing prognostic models, and continuing research efforts to elucidate its pathobiology and pathogenesis.

Objective.—To summarize updated information and provide a general overview of the clinicopathologic features, pathobiology, and cytogenetic and molecular pathogenesis of MDSs.

Data Sources.—Relevant articles indexed in PubMed (National Library of Medicine) between 1982 and 2005 and reference medical texts.

Conclusions.—Although MDSs remain a relatively poorly defined disease entity, recent advancements in cytogenetic and molecular studies have significantly contributed to our present knowledge of MDSs. Novel strategies for studying the pathogenesis and evolution of MDSs continue to shape our understanding of this disease and guide our approaches to diagnosis and treatment.
Recognition of Histopathologic Patterns of Diffuse Malignant Mesothelioma in Differential Diagnosis of Pleural Biopsies
Authors: Allen Timothy Craig
Published: February 2021

Context.—Diffuse malignant mesothelioma is generally divided into 3 basic histologic types—epithelial, biphasic, or sarcomatous. However, a great diversity of histologic patterns exists within these 3 basic histologic types.

Design.—The diverse histologic patterns of diffuse malignant mesothelioma are briefly described, including infrequently encountered patterns.

Results. The histologic patterns of diffuse malignant mesothelioma provide a wide variation of features for the pathologist to consider in the differential diagnosis of a pleural biopsy.

Conclusion.—Pathologists should be aware of the varied histologic patterns of diffuse malignant mesothelioma when evaluating pleural biopsies.
The Italian Quality Control Scheme for Crossmatching Procedures and HLA Sera Screening: The 2002 Pilot Study
Authors: Conca Raffaele , Praticò-Barbato Loredana , Dall'Omo Anna Maria , Amoroso Antonio
Published: February 2021

Context.—The first national quality control (QC) program of histocompatibility serum testing was performed in Italy in 2002.

Objective.—To monitor the performance of HLA typing laboratories while meeting the accreditation requirements of the European Federation for Immunogenetics (EFI), which require HLA typing laboratories to participate in external QC of their crossmatch and antibody analyses.

Design.—The Turin Transplant Immunology Service was asked to organize a QC survey of 17 HLA typing laboratories in Italy. Each laboratory received 12 serum specimens and 6 blood samples and was required to perform 36 crossmatches and 12 serum antibody specificity determinations.

Settings.—Data of participating centers were compared to establish whether EFI requirements were satisfied.

Results.—In crossmatch analysis, the results of 32 of 36 crossmatches reached the 75% consensus target, with all the participating laboratories meeting the standards of the EFI. In antibody analysis, only 7 of 17 laboratories met the EFI standards.

Conclusion.—The first Italian QC program shows that the participating laboratories obtained consistent results in crossmatching, whereas the results were less satisfactory in the determination of serum antibody specificity, where consensus was reached only with monospecific sera and antibody-negative samples.
Clear Cell Myomelanocytic Tumor (PEComa) of the Duodenum in a Child With a History of Neuroblastoma
Authors: Mhanna Tony , Ranchere-Vince Dominique , Hervieu Valérie , Tardieu Dominique , Scoazec Jean-Yves , Partensky Christian
Published: February 2021

We report herein a case of digestive clear cell myomelanocytic tumor (PEComa) that is unique in its location and presentation. The lesion, located in the duodenal wall, was diagnosed in a child with a history of cervical neuroblastoma that was in remission after surgical resection and chemotherapy. The diagnosis was obtained by examination of a biopsy specimen taken during laparoscopy. The decision was made to perform surgical resection. Examination of the surgical specimen confirmed the diagnosis of PEComa. No metastasis was found. After 2 years of follow-up, the patient is alive, without evidence of metastasis or recurrence. This case highlights the distinctive characteristics of the cells in PEComa, recognizable even on limited biopsy material. It also suggests a possible association between PEComa and neuroblastoma, 2 unusual tumors that belong to the spectrum of lesions known to occur in patients with tuberous sclerosis and that may share a possible common pathogenetic mechanism.
Detection and Correction of Systematic Laboratory Problems by Analysis of Clustered Proficiency Testing Failures
Authors: Hoeltge Gerald A. , Phillips Mari Gina , Styer Patricia E. , Mockridge Peter
Published: February 2021

Context.—The Laboratory Accreditation Program of the College of American Pathologists monitors the performance of its subscribers in proficiency testing (PT). Failure to perform as expected prompts the program to query the laboratory.

Objective.—To determine whether laboratories are correcting apparent problems when contacted by the program about repeatedly unacceptable performance in a diagnostic test.

Design.—Retrospective analysis of 1 year's records (2002–2003) from the College's Proficiency Testing Exception Summary correspondence, which identifies clusters of PT failures. The analysis focused on those laboratories in which the Proficiency Testing Exception Summary algorithm identified repeated failures over 3 or 4 testing events; PT performance is monitored as a condition of accreditation. During 1 survey year, approximately 6300 accredited laboratories collectively tested approximately 1 205 000 analytes and submitted results to their PT providers on more than 3 500 000 PT challenges. During the period of observation, 14 085 Proficiency Testing Exception Summary reports were mailed to participants. Educational materials were included to help laboratories identify and correct each PT failure.

Results.—There were only 1304 cases of repeated PT failures after the initial correspondence from the accreditation program (9.3%). Of these, there were only 119 cases of unsatisfactory results on the subsequent PT event (9.1%). All systematic problems were resolved by the conclusion of the third round of correspondence.

Conclusions.—Accredited laboratories generally perform well in proficiency testing. Identification of clusters of PT failures by the accreditation provider can help those laboratories having analytic difficulties to investigate and correct the problems.
Primary Localized Laryngeal Amyloidosis: Report of 3 Cases With Long-term Follow-up and Review of the Literature
Authors: Ma Linglei , Bandarchi Bizhan , Sasaki Clarence , Levine Steven , Choi Young
Published: February 2021

Context.—Localized laryngeal amyloidosis is an uncommon condition with limited long-term follow-up studies. The precise etiology and pathogenesis are not entirely clear.

Objective.—To further characterize the histopathologic features and possible pathogenesis of localized laryngeal amyloidosis.

Design.—Three cases of primary localized laryngeal amyloidosis were identified at our institutions from 1980 to 2003. The clinical features and histologic and immunohistochemical patterns were evaluated. Systemic workups were pursued during the long-term follow-up.

Results.—The common presentation of the patients was hoarseness. The lesions involved vocal cords, anterior commissure, and ventricle. Microscopically, the amyloid was present within the submucosa with an adjacent lymphoplasmacytic infiltrate. The plasma cells and amyloid demonstrated monoclonal light chain restriction in all 3 cases (2 λ, 1 κ). No evidence of systemic amyloidosis or an overt B-cell lymphoma was found in these patients. Two patients with long-term follow-up underwent subsequent surgical removals for multiple recurrences, which occurred within 1 year of the initial diagnosis.

Conclusions.—The demonstration of monoclonal light chain expression in the plasmacytic infiltrate and amyloid component in the absence of systemic lymphomas indicates that localized laryngeal amyloidosis may represent a form of benign monoclonal plasma cell dyscrasia. A close follow-up of the patients may be indicated for early detection of recurrences.
Errors and Error Rates in Surgical Pathology: An Association of Directors of Anatomic and Surgical Pathology Survey
Authors: Cooper Kumarasen
Published: February 2021

This survey on errors in surgical pathology was commissioned by the Association of Directors of Anatomic and Surgical Pathology Council to explore broad perceptions and definitions of error in surgical pathology among its membership and to get some estimate of the perceived frequency of such errors. Overall, 41 laboratories were surveyed, with 34 responding to a confidential questionnaire. Six small, 13 medium, and 10 large laboratories (based on specimen volume), predominantly located in the United States, were surveyed (the remaining 5 laboratories did not provide this particular information). The survey questions, responses, and associated comments are presented. It is clear from this survey that we lack uniformity and consistency with respect to terminology, definitions, and the identification/documentation of errors in surgical pathology. An appeal is made for the urgent need to reach some consensus in order to address these discrepancies as we prepare to combat the issue of errors in surgical pathology.