bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucocutaneous Angiomyolipoma
Authors: Watanabe Kazuo , Suzuki Toshimitsu
Published: January 2021

Objective.—Angiomyolipoma (AML) is a distinctive tumor that usually occurs in the kidney and rarely in the liver. Angiomyolipoma of other sites is extremely rare, and, to our knowledge, only 2 cases have been described in the nasal cavity. We present 2 additional cases of AML of the nasal cavity and discuss the difference between them and renal AML.

Case Reports and Pathologic Findings.—Two tumors in a 66-year-old man and an 88-year-old woman without tuberous sclerosis are described. They showed 20-mm, well-circumscribed, polypoid shapes. Histologically, they were composed of mature smooth muscle cells, fat cells, and various-sized blood vessels. In addition, aggregated small lymphocytes were noted. Neither epithelioid smooth muscle cells nor HMB45 immunoreactivity was seen in either case.

Conclusions.—The clinicopathologic features of AML of the nasal cavity are distinct from renal and hepatic AML and are common to those of AML arising in the skin and oral and pharyngeal mucosa. The term mucocutaneous angiomyolipoma is thought to be appropriate to express these characteristic tumors.
Histopathologic Features and MIB-1 Labeling Indices in Recurrent and Nonrecurrent Meningiomas
Authors: Abramovich Caroline M. , Prayson Richard A.
Published: January 2021

Background.—Predicting the behavior of meningiomas based on histopathologic features alone has remained problematic.

Design.—This study retrospectively compared several histopathologic features and MIB-1 labeling indices (LIs) in recurrent meningiomas with those of nonrecurrent meningiomas. Six histopathologic features, including mitoses, necrosis, loss of architectural pattern, hypervascularity/hemosiderin deposition, prominent nucleoli, and nuclear pleomorphism, were compared between 32 recurrent and 27 nonrecurrent meningiomas using Fisher exact tests. MIB-1 LIs (% positive tumor cell nuclei) were compared using the Wilcoxon rank sum test.

Results.—The patients in the recurrent group included 26 women (mean age, 55 years), who developed 1 to 5 recurrences. Time intervals to the first recurrence ranged from 5 to 183 months (mean, 55 months). The nonrecurrent group included 21 women (mean age, 56 years), with follow-up ranging from 88 to 124 months (mean, 109 months). Of the histopathologic features evaluated, statistically significant differences between the recurrent and nonrecurrent groups were found only with respect to prominent nucleoli (P = .024) and nuclear pleomorphism (P < .001), both of which were more common in the recurrent group. In the recurrent group, 9 tumors were considered malignant (defined by brain invasion or metastasis) versus 2 of the nonrecurrent meningiomas. Nineteen percent of nonrecurrent tumors versus 41% of recurrent tumors had 2 or more of the 6 histopathologic features. MIB-1 LIs in the nonrecurrent group ranged from 0 to 8.3 (mean, 1.5) and were generally lower than those in the recurrent group (range, 0–32.5; mean, 5.4); no statistical difference was identified between these groups. No statistically significant difference with regard to histology or MIB-1 LIs was noted between the initially excised recurrent tumor and the most recently resected recurrence.

Conclusions.—Of the histopathologic features examined, only prominent nucleoli and nuclear pleomorphism were found to be statistically more common in recurrent than nonrecurrent meningiomas. The mean MIB-1 LI was higher in the recurrent than in the nonrecurrent group, although there was no statistical difference between means and there was clear overlap with regard to MIB-1 LI ranges.
Performance of a Fluid-Based, Thin-Layer Papanicolaou Smear Method in the Clinical Setting of an Independent Laboratory and an Outpatient Screening Population in New England
Authors: Díaz-Rosario Luis A. , Kabawat Salim E.
Published: January 2021

Background.—A patented, fluid-based, thin-layer method for preparation of Papanicolaou (Pap) smears (ThinPrep Pap test) has been reported to be significantly more effective than the conventional smear invented by George Papanicolaou. We tested this position by comparing the cytologic diagnosis and specimen adequacy results obtained using the ThinPrep method with data from conventional Pap smears obtained from a similar population.

Methods.—Test results of 56 339 ThinPrep specimens were compared with results from 74 756 conventional smear cases obtained from the same sources in a corresponding period of the previous year.

Results.—The use of ThinPrep for cervicovaginal cytology produced a 75.14% increase in the detection of low-grade squamous intraepithelial lesions and higher diagnoses. Detection of low-grade squamous intraepithelial lesions increased by 71.65% (from 1.58% to 2.71%), and detection of high-grade squamous intraepithelial lesions increased by 102.54% (from 0.26% to 0.52%). There was a 39.11% decrease in the atypical squamous cells of undetermined significance–intraepithelial lesion ratio (from 2.07 to 1.26). There were also marked decreases in the number of specimens categorized as “satisfactory but limited,” owing to obscuring inflammation (−94.34%), obscuring blood (−99.84%), and poor fixation (−99.25%).

Conclusion.—ThinPrep produced increased detection of premalignant precursors while improving specimen adequacy.
Infectious Mononucleosis in an Outpatient Population
Authors: Brigden Malcolm L. , Au Sandra , Thompson Susan , Brigden Sean , Doyle Patrick , Tsaparas Yotis
Published: January 2021

Objectives.—To determine the sensitivity and specificity of 2 modern hematology analyzers in flagging heterophile-positive patients; to determine if heterophile-positive, instrument-flagged specimens contain a larger number or a different spectrum of atypical lymphocytes; to document the overall sensitivity and specificity of Hoagland's morphologic criteria in identifying heterophile-positive patients in an outpatient population with a clinical diagnosis of mononucleosis; and to examine whether individual morphologic features might aid in the diagnosis of suspected infectious mononucleosis.

Design.—A prospective study of patients referred with a clinical diagnosis of infectious mononucleosis who subsequently tested positive for the heterophile antibody. The control group consisted of a similar population of patients who tested negative for the heterophile antibody.

Intervention.—Hematology profiles of peripheral blood samples were determined with Coulter STKS and Sysmex NE-8000 analyzers. A corresponding Wright-Giemsa–stained blood smear was subsequently examined by a single skilled technologist, who performed a 200-cell white blood cell differential and a 200-cell lymphocyte differential. A specific morphologic search was made for the presence of smudge cells or lymphocytes with cloverleaf nuclei.

Results.—Using a combination of all flagging criteria, the 2 analyzers identified 156 (86.2%) of 181 heterophile-positive patients as meriting further review. The sensitivity and specificity values of the Coulter analyzer in predicting positive heterophile status for the blast flag were 41% and 97.1%, respectively; for the variant lymphocyte flags, 72.4% and 79.1%, respectively; and for both flags, 40% and 98.1%, respectively. For the Sysmex analyzer, the sensitivity and specificity values in predicting positive heterophile status for the blast flag were 43.4% and 88.6%, respectively; for the variant lymphocyte flag, 15.8% and 90.8%, respectively; and for both flags, 10.5% and 96%, respectively. Considering the classic criteria developed by Hoagland, a lymphocytosis of at least 50% was present in 120 (66.3%) heterophile-positive patients, while an atypical lymphocytosis of at least 10% of the total WBC count was noted in 135 patients (74.6%). The sensitivity and specificity values of a lymphocytosis ≥50% for diagnosing heterophile-positive status were 66.3% and 84.5%, respectively, while the sensitivity and specificity of an atypical lymphocytosis ≥10% were 74.6% and 92.3%, respectively. The presence of smudge cells or cloverleaf lymphocyte nuclei was verified as having high specificity but low sensitivity for suggesting a diagnosis of infectious mononucleosis.

Conclusion.—Although a number of patients did not meet Hoagland's criteria for the diagnosis of infectious mononucleosis, the flagging systems of modern hematology analyzers successfully identified most cases as requiring further review.
Glomus Coccygeum in Surgical Pathology Specimens
Authors: Gatalica Zoran , Wang Liqiang , Lucio Emmanuel T. , Miettinen Markku
Published: January 2021

Background.—Rarely encountered nonpathologic structures may pose diagnostic problems and cause unnecessary special investigations. More importantly, however, they may be falsely accused as culprits in unrelated pathologic processes. Glomus coccygeum is one such structure. Glomus bodies (including coccygeal glomus) consist of modified smooth muscle cells arranged in layers around small vascular channels. When found in distal extremities, they generally do not represent a diagnostic problem; however, large glomus bodies present in a pericoccygeal location (glomus coccygeum) may cause significant problems for a surgical pathologist unfamiliar with this structure.

Design.—We reviewed 37 coccygeal bones removed during rectal resection for carcinoma (rectal and uterine) and for various other reasons, among which was a single case of coccygodynia. Immunohistochemical and ultrastructural examinations were performed in selected cases.

Results.—Sharply circumscribed glomus bodies composed of various proportions of glomus cells without atypia or pleomorphism and without expansile growth or infiltration of surrounding soft tissue or bone were identified in 50% of cases. Size varied significantly (maximum 4 mm), but paradoxically the smallest glomus body (less than 1 mm) was found in the case of coccygodynia. Glomus coccygeum posed a significant diagnostic challenge to the pathologists involved in these cases, as the retrospective review found that it was diagnosed correctly in only 3 cases.

Conclusions.—Glomus coccygeum is a nonpathologic structure that exhibits significant variation in size and proportion of the constitutive elements. Immunohistochemical demonstration of smooth muscle actin and neuron-specific enolase in glomus cells may be beneficial for accurate identification of this organelle.
Focus of Signet Ring Cell Carcinoma in an Adenoma of the Sigmoid Colon
Authors: Tandon Manish , Sostek Mark , Klein Michael A.
Published: January 2021

A case of a pedunculated adenomatous polyp of the sigmoid colon was found to have a primary focus of signet ring cell carcinoma. Histologic examination of the medium-sized polyp was consistent with an adenoma to carcinoma sequence for signet ring cell carcinoma of the colon, similar to that for the common adenocarcinomas.
Familial Occurrence of Acinic Cell Carcinoma of the Parotid Gland
Authors: Depowski Peter L. , Setzen Gavin , Chui Alex , Koltai Peter J. , Dollar James , Ross Jeffrey S.
Published: January 2021

We report the familial occurrence of acinic cell carcinoma involving the parotid gland, the first such report of which we are aware. The familial occurrence of any salivary gland neoplasm is rare. Several reports are present in the literature, including pleomorphic adenoma, Warthin tumor, carcinoma of the submandibular gland, and malignant lymphoepithelial lesion. We report the case of a 35-year-old man who underwent excision of a left parotid gland acinic cell carcinoma. Eight years later, his daughter presented at the age of 16 years with a nontender parotid gland mass that was excised and found also to be acinic cell carcinoma. The histologic features of both neoplasms were typical of acinic cell carcinoma. While this may represent a coincidental event, the possibility that this familial occurrence is a manifestation of common genetic or environmental risk cannot be excluded.
Optimization of an Automated DNA Purification Protocol for Neonatal Screening
Authors: Heath Ellen M. , O'Brien Darin P. , Banas Richard , Naylor Edwin W. , Dobrowolski Steven
Published: January 2021

Context.—Collection of blood from newborns is a standard clinical procedure used for genetic screening. Typically, blood from a heel prick is absorbed onto standard collection paper and dried before analysis of metabolites, proteins, hormones, and more recently DNA.

Objective.—To evaluate strategies to purify DNA for use with automated workstations.

Design.—Two factors were used to evaluate several DNA purification protocols: residual heme contamination and amplification yield. The protocol that produced DNA with the lowest heme content and the highest amplification yield was selected. In combination with those two performance factors, the protocol with the fewest number of steps was chosen to reduce reagent use and processing time.

Setting.—Industrial research and development laboratory.

Results.—Robust amplification of DNA isolated from dried blood spots was demonstrated using both fluorescence and agarose gel–based detection methods. In addition, the samples had consistent DNA volumes and had no detectable cross-contamination. Suggested instrument settings, equipment, and supplies were included for automated processing of DNA from dried blood spots.

Conclusion.—A 4-step DNA processing protocol was developed for dried blood spots. The protocol could be performed in either a manual or automated format, making it possible to process hundreds of samples in 1 day.
Amplification of Padlock Probes for DNA Diagnostics by Cascade Rolling Circle Amplification or the Polymerase Chain Reaction
Authors: Thomas David C. , Nardone Glenn A. , Randall Sandra K.
Published: January 2021

Context.—Padlock probes are highly specific reagents for DNA diagnostics that can discriminate gene sequences with single base mutations. When the 3′ and 5′ terminal regions of the oligonucleotide probes are juxtaposed on a target DNA sequence, they can be circularized by enzymatic ligation and become topologically locked to the target. However, to be useful in solution-based diagnostics, the sensitivity of padlock probes must be markedly enhanced.

Objective.—To describe two methods for geometric amplification of circularized padlock probes.

Design.—Cascade rolling circle amplification is an isothermal system that uses generic primers and a DNA polymerase with strong strand displacement activity to amplify circularized probes by a mechanism combining rolling circle replication and strand displacement synthesis. One of the primers was designed as an energy transfer–labeled primer, which generates a fluorescence signal only when incorporated into the amplified product, enabling a direct means of detection.

Results.—Using pUC19 as a model target to circularize an 89-base probe, a 10 billion–fold amplification was achieved with Bst DNA polymerase (large fragment) within 1 hour starting with as few as 10 probe molecules. The polymerase chain reaction was also used to amplify ligated padlock probes in a rare target detection system. In mixing experiments containing both normal and mutant p53 or c-Ki-ras2 gene target sequences, mutant targets were easily detected in the presence of a 500-fold excess of normal target copies.

Conclusion.—These results indicate that padlock probes can be amplified to the high levels required for solution-based DNA diagnostics.
HFE Genotyping Using Multiplex Allele-Specific Polymerase Chain Reaction and Capillary Electrophoresis
Authors: Lubin Ira M. , Yamada N. Alice , Stansel Rachel M. , Pace Rhonda G. , Rohlfs Elizabeth M. , Silverman Lawrence M.
Published: January 2021

Context.—Hereditary hemochromatosis is recognized as one of the most common autosomal recessive disorders, with a prevalence of 1 in 200 to 400 in the white population. Early detection and treatment are completely effective in preventing pathology. It is anticipated that testing for hereditary hemochromatosis will increase, as will the need for a technology that can handle the demand.

Objective.—To describe a high-throughput, single-tube, allele-specific multiplex polymerase chain reaction assay for identifying the 2 mutations in the HFE gene associated with hereditary hemochromatosis.

Design.—Fluorescence-labeled polymerase chain reaction products from a multiplex polymerase chain reaction are analyzed by automated capillary electrophoresis.

Data Analysis.—The assay was validated by analysis of 25 blinded samples, and results were concordant with an established laboratory assay.

Conclusion.—The assay described offers a significant improvement over manual laboratory assays in throughput, reduced technologist time, and cost.
Primary Cutaneous T-Cell–Rich B-Cell Lymphomas With Flow Cytometric Immunophenotypic Findings
Authors: Dunphy Cherie H. , Nahass George T.
Published: January 2021

Background.—Primary cutaneous T-cell–rich B-cell lymphoma is a relatively rare entity that has been diagnosed most commonly using immunohistochemical and molecular techniques. Flow cytometric immunophenotyping (FCI) has not been described in this entity. We report the demonstration of B-cell monoclonality by FCI in 3 cases of primary cutaneous T-cell–rich B-cell lymphoma.

Methods.—Clinical and pathologic data were recorded for 3 cases of primary cutaneous T-cell–rich B-cell lymphoma. Immunohistochemical and FCI data were available in all cases; DNA analysis was performed in 1 case.

Results.—Flow cytometric immunophenotyping revealed a monoclonal B-cell population exclusively in the monocyte (large cell) region in all 3 cases. Immunohistochemistry confirmed the T-cell richness of the infiltrates within the cutaneous lymphomas; T cells accounted for 65% to greater than 90% of the cells within the infiltrates. DNA analysis by polymerase chain reaction in 1 case did not demonstrate a monoclonal rearrangement of the immunoglobulin heavy-chain gene.

Conclusions.—Flow cytometric immunophenotyping in primary cutaneous T-cell–rich B-cell lymphoma may be useful in demonstrating monoclonality in these cases, especially if there is selective gating on the relatively small population of cells in the large cell region. The FCI data should be correlated with histology and immunohistochemistry.
Expression of bcl-2 in Enteric Neurons in Normal Human Bowel and Hirschsprung Disease
Authors: Wester Tomas , Olsson Yngve , Olsen Leif
Published: January 2021

Objective.—The bcl-2 protein has the functional role of blocking apoptosis, ie, programmed cell death. This protein is widely expressed in the developing central and peripheral nervous systems. The purpose of this study was to map bcl-2 expression in the human enteric nervous system, as this has not previously been done.

Methods.—Rectal specimens were obtained at autopsy of 13 fetuses at 13 to 31 weeks of gestation. Normal colon was also obtained from 5 children and 2 adults, and, in addition, ganglionic and aganglionic bowel resected in 11 patients with Hirschsprung disease was examined. Specimens were fixed in formalin, embedded in paraffin, and analyzed with immunohistochemical methods, using antibodies raised against bcl-2 and neuron-specific enolase (NSE).

Results.—The bcl-2 protein was expressed in myenteric and submucous ganglion cells in fetuses, children, and adults. Nerve fibers of the enteric plexuses that were bcl-2 immunoreactive were few compared with the number of NSE-immunoreactive nerve fibers. In aganglionic bowel no bcl-2–or NSE-immunoreactive ganglion cells were revealed. Results of NSE immunohistochemistry showed clearly stained hypertrophic nerve bundles, known to be of extrinsic origin, which were only weakly bcl-2 immunoreactive.

Conclusion.—Expression of bcl-2 in enteric ganglion cells of the myenteric and submucous plexuses is displayed in the fetus and during childhood and is also retained in adult bowel. Immunohistochemical analysis of bcl-2 provides a good marker for identification of ganglion cells in Hirschsprung disease and may also be valuable for the diagnosis of disorders characterized by hypoganglionosis or hyperganglionosis.
Protocols for the Examination of Tumors of Diverse Sites
Authors: Hammond M. Elizabeth H. , Compton Carolyn C.
Published: January 2021

This issue of the Archives includes previously unpublished protocols for the examination of specimens removed from patients with cancer of diverse sites. We provide a historical context for the development of these protocols and describe the process of development and approval. General information about the structure and content of the protocols is also provided. Cancer protocol development is an important step in the process of standardized cancer reporting. The value of such standardized reporting is discussed.
Protocol for the Examination of Specimens From Patients With Hepatocellular Carcinoma and Cholangiocarcinoma, Including Intrahepatic Bile Ducts
Authors: Ruby Stephen G.
Published: January 2021

No Abstract Available
Terminal Deoxynucleotidyl Transferase–Negative Acute Lymphoblastic Leukemia
Authors: Faber Joana , Kantarjian Hagop , Roberts W. Mark , Keating Michael , Freireich Emil , Albitar Maher
Published: January 2021

Objective.—Terminal deoxynucleotidyl transferase (TdT) is a useful marker in the diagnosis of acute lymphoblastic leukemia (ALL) (French-American-British [FAB] L1 and L2) and is most useful in distinguishing ALL from mature B-lymphoid neoplasms, such as Burkitt lymphoma (FAB L3) and other lymphoid malignancies. The frequency of TdT-negative ALL is not known. Here we report 3 TdT-negative ALL cases that met the criteria for T-cell ALL.

Design.—We reviewed approximately 200 cases of ALL retrieved from the database at our institution. All cases were evaluated using Wright-Giemsa, myeloperoxidase, butyrate, and TdT staining; immunophenotyped using flow cytometry; and studied using Southern blot analyses for T-cell receptors and immunoglobulin gene rearrangement.

Results.—All ALL cases (L1 and L2) were TdT-positive, except for 3 cases that were of early T-cell lineage. None of the 3 cases demonstrated positivity for TdT in immunofluorescence staining with polyclonal antibodies or flow cytometry with monoclonal antibodies. Flow cytometric analysis confirmed a pre–T-cell immunophenotype in all 3 cases. One of the cases showed rearrangement of a T-cell antigen receptor and immunoglobulin heavy chain (JH). A second case showed germline configuration of T-cell receptors, but also showed rearrangement of the JH, despite the expression of T-cell markers only.
Mucoepidermoid Carcinoma Arising in the Glans Penis
Authors: Layfield Lester J. , Liu Katharine
Published: January 2021

Mixed carcinoma (squamous and glandular) of the penis is a rare neoplasm with an unknown origin and a poorly defined prognosis. The mucoepidermoid carcinoma described herein has not been previously reported to our knowledge. The present carcinoma arose from and extensively ulcerated the squamous epithelium of the glans penis, including that surrounding the urethral meatus. The neoplasm was composed of well-differentiated nonkeratinizing squamous cell carcinoma associated with large areas of carcinoma formed by cell nests that contained poorly differentiated squamous elements and large eosinophilic to pale granular cells. Mucin stains revealed approximately one quarter of the pale cells contained mucous substances. These findings are virtually identical to the mucoepidermoid type of carcinoma seen in the cervix. The 3 previously reported cases of adenosquamous carcinoma of the penis demonstrated a relatively indolent course, with only one being associated with a single inguinal lymph node metastasis. That patient was alive and well 9 years following diagnosis. Our example of mucoepidermoid carcinoma appears to demonstrate a more aggressive course than those reported previously.
p53, ErbB2, and TAG-72 Expression in the Spectrum of Ductal Carcinoma In Situ of the Breast Classified by the Van Nuys System
Authors: Kanthan Rani , Xiang Jim , Magliocco Anthony M.
Published: January 2021

Context.—The Van Nuys (VN) classification system for ductal carcinoma in situ (DCIS) of the breast is a simplified morphology-based system that uses the presence of nuclear pleomorphism and comedo-type necrosis to stratify DCIS lesions into 3 prognostic groups.

Objective.—To determine if there is an underlying biological basis that correlates with the morphologic aspects of the VN classification system.

Design.—We evaluated the expression of markers implicated in the development of breast cancer (p53, ErbB2, and TAG-72) in DCIS classified with the VN system. Forty-five cases of pure DCIS were classified as 8 cases of VN1, 7 cases of VN2, and 30 cases of VN3. p53, ErbB2, and TAG-72 antigen expression was measured by immunohistologic means in each of the cases.

Results.—Nuclear accumulation of p53 was only observed in VN3 (30%). ErbB2 overexpression was found only in VN2 (14%) and VN3 (43%). TAG-72 expression was observed in all categories of lesions but was more frequent in VN2 (71%) and VN3 (70%) compared with VN1 (25%). It appears that overexpression of ErbB2 and p53 are features associated with the high-grade lesions.

Conclusion.—The simplified VN classification system for DCIS has a clear underlying biological basis as evidenced by differential expression of tumor-associated antigens in each of the 3 morphologic categories. These differences may contribute to the differential clinical behavior of the separate groups.
Detection of Indinavir Crystals in Urine
Authors: Hortin Glen L. , King Christine , Miller Kirk D. , Kopp Jeffrey B.
Published: January 2021

Objectives.—To determine the frequency of crystalluria in patients treated with the human immunodeficiency virus protease inhibitor indinavir and to compare methods of detecting crystalluria.

Methods.—A total of 308 freshly voided urine specimens from 168 patients treated with indinavir were evaluated by manual microscopy of sediment and microscopy with an automated workstation and by dipstick analysis.

Results.—Crystals were detected in 22%, 31%, or 32% of specimens using, respectively, an automated workstation, manual microscopy, or both methods. Proteinuria or hemoglobinuria occurred significantly more often in specimens with (28%) than without (18%) crystals. Frequency of crystalluria was unrelated to specific gravity, but it increased at higher pH. Crystals were detected in 21% of specimens with pH less than 6 and 42% of specimens with pH of 6 or higher.

Conclusions.—Crystalluria occurs in more than 30% of urine specimens from patients treated with indinavir, but detection rates vary substantially with method of analysis. Manual microscopy detected crystalluria 41% more often than did an automated workstation.
Mediastinal Atypical Carcinoid and Neurofibromatosis Type 1
Authors: Mathew Paul , Roberts Jeffrey A. , Zwischenberger Joseph , Haque Abida K.
Published: January 2021

We report a case of mediastinal atypical carcinoid in a 63-year-old woman with neurofibromatosis type 1 (NF-1), who presented with shortness of breath and a bulky mediastinal mass. Initial consideration was given to a neurogenic tumor. However, on thoracoscopic biopsy, the histologic appearance was consistent with an atypical carcinoid. Carcinoid tumors have been reported in association with NF-1 previously, but commonly in such unusual sites as the ampulla of Vater and duodenum and not in the thorax. The bulky, extensive, and highly vascular nature of the lesion precluded resection or debulking surgery. To our knowledge, there are no previous reports of atypical carcinoid of the lung or mediastinum in a patient with neurofibromatosis. This case report, therefore extends the spectrum of solid neoplasia in general and carcinoid tumors in specific, as they occur in association with NF-1.
Comparative Pathology
Authors: Smith Albert C.
Published: January 2021

Marine animals offer unparalleled diversity in form, behavior, environments occupied, and other attributes. Furthermore, certain of these animals have evolutionary links to humans. These features make marine animals of special interest to comparative and human pathologists. This article focuses on comparative aspects of 4 major disorders, namely, tumors, immunologic disorders, vascular pathology, and anatomic malformations.
Thyroid Sclerosing Mucoepidermoid Carcinoma With Eosinophilia
Authors: Solomon Alyson C. , Baloch Zubair W. , Salhany Kevin E. , Mandel Susan , Weber Randal S. , LiVolsi Virginia A.
Published: January 2021

We present the clinical and pathologic findings of a case of sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid in a 39-year-old woman. This particular case is notable because it initially presented as a cervical lymph node metastasis, and the initial clinical and histologic impression was Hodgkin disease, nodular sclerosis type. Sclerosing mucoepidermoid carcinoma with eosinophilia is a differentiated malignant neoplasm of the thyroid that can be confused with anaplastic carcinoma, medullary carcinoma, squamous cell carcinoma, or, as in this case, Hodgkin disease. A correct diagnosis of sclerosing mucoepidermoid carcinoma with eosinophilia involves awareness of this entity and appropriate immunohistochemical analysis. In this article, we briefly review the literature and stress the histologic and cytologic findings characteristic of sclerosing mucoepidermoid with eosinophilia of the thyroid.
Carcinoid-Related Angiomatous Polyposis Simulating Crohn Disease
Authors: Vesoulis Z. , Abrahams Neil , Becker John , Slezak Fred
Published: January 2021

Polyposis associated with ileal carcinoid tumors is a rarely described pathologic mucosal transformation that may simulate inflammatory or neoplastic polyps. We describe a case with innumerable sessile polyps and groups of large filiform-like polyps of the terminal ileum associated with submucosal carcinoid tumors and a large mesenteric carcinoid tumor mass. The clinical, radiographic, and endoscopic presentation of the polyposis, together with the presence of multiple small bowel stenotic lesions, simulated Crohn disease. We propose the descriptive terminology angiomatous polyposis to describe the striking microscopic vascular proliferation that characterizes these polyps. The distribution of these lesions, with the most profuse polyposis in the immediate proximity of the carcinoid nests, and the immunohistochemical demonstration of growth factor substances, such as transforming growth factor α within neoplastic cells and adjacent polyps, suggest a tumor factor–mediated stromal proliferation.
Basaloid Squamous Cell Carcinoma Occurring in the Urinary Bladder
Authors: Vakar-López Funda , Abrams Jacki
Published: January 2021

Basaloid squamous cell carcinoma is a recently described, distinct variant of squamous cell carcinoma that arises predominantly in the upper aerodigestive tract. Herein we report a case of basaloid squamous cell carcinoma arising in the urinary bladder. The patient was a 60-year-old woman who experienced intractable urinary tract infections following multiple corrective surgical procedures for incontinence. Biopsies of cystoscopically evident flat lesions were performed, and the patient subsequently underwent a radical cystectomy. Histologically, the lesions consisted of nests of basaloid cells with brisk mitotic activity, areas of squamous differentiation along with areas of squamous metaplasia, and squamous cell carcinoma in situ. These features are similar to those of basaloid squamous cell carcinoma described elsewhere in the body. To our knowledge, this is the first reported case of basaloid squamous cell carcinoma in the urinary bladder.
Can Polymerase Chain Reaction Help Distinguish Benign From Malignant Lymphoid Aggregates in Bone Marrow Aspirates?
Authors: Ben-Ezra Jonathan , Hazelgrove Kirk , Ferreira-Gonzalez Andrea , Garrett Carleton T.
Published: January 2021

Objective.—Although morphologic and immunologic clues are helpful in distinguishing benign from malignant lymphoid aggregates in bone marrow biopsies, there remain some cases in which it is not possible to arrive at a definitive diagnosis. Since the malignant aggregates are monoclonal B-cell proliferations, we sought to determine whether performing polymerase chain reaction for the immunoglobulin heavy-chain locus would be helpful in distinguishing these 2 entities.

Methods and Results.—Scrapings from unstained bone marrow aspirate smears or touch preparations of bone marrow biopsies from 15 patients with benign bone marrow lymphoid aggregates and 18 patients with malignant lymphoid infiltrates were analyzed for rearrangements of the FR3 region of the immunoglobulin heavy-chain gene locus by a heminested polymerase chain reaction procedure. All specimens had amplifiable DNA, as shown by amplification of the ras proto-oncogene. None of the 15 cases of benign bone marrow lymphoid aggregates demonstrated clonality upon amplification of the immunoglobulin heavy-chain gene locus. In contrast, 8 of the 18 malignant samples were positive (P = .01 by χ2 test; sensitivity, 44%; specificity, 100%; positive predictive value, 100%; negative predictive value, 60%). There was a tendency for there to be more lymphocytes in stained bone marrow aspirate smears from the cases of malignant lymphoid aggregates with a positive polymerase chain reaction result than in those without demonstrable clonality (36.0 ± 35.4% vs 9.8 ± 8.0%, P = .13).

Conclusions.—Polymerase chain reaction for the immunoglobulin heavy-chain gene locus may help distinguish benign from malignant bone marrow lymphoid aggregates. Although the presence of false-negative samples may be related to the relative lack of lymphocytes in the bone marrow aspirates, other factors, such as the lack of amplification of the FR3 region of the immunoglobulin heavy-chain gene locus in particular tumors, cannot be ruled out with certainty.
Differential Distribution of the Neuron-Associated Class III β-Tubulin in Neuroendocrine Lung Tumors
Authors: Katsetos Christos D. , Kontogeorgos George , Geddes Jennian F. , Herman Mary M. , Tsimara-Papastamatiou Hera , Yu Yunxia , Sakkas Lazaros I. , Tsokos Maria , Patchefsky Arthur S. , Ehya Hormoz , Cooper Harry S. , Provencio Javier , Spano Anthony J. , Frankfurter Anthony
Published: January 2021

Objective.—To study the immunoreactivity profile of the neuron-associated class III β-tubulin isotype (β III) in epithelial lung tumors.

Design.—One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti–β III mouse monoclonal antibody (TuJ1) and an anti–β III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined.

Results.—In the fetal airway epithelium, β III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. β III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, β III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non–small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of β III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal β III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary. β III is expressed to a much lesser extent in atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of β III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors.

Conclusions.—In the context of neuroendocrine lung tumors, β III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, β III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non–small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, β III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of β III phenotypes in non–small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation.
Pseudomembranous Gastritis
Authors: Yong Sherri , Attal Houssam , Chejfec Gregorio
Published: January 2021

A 36-year-old Hispanic man who had undergone allogeneic bone marrow transplantation, complicated by graft versus host disease, was admitted with acute gastrointestinal symptoms, including severe diarrhea and diffuse abdominal pain. He also had a persistent cough with sputum production. Blood cultures yielded Escherichia coli, and sputum cultures grew Apergillus species. The patient was treated with antifungal agents and broad-spectrum antibiotics. Despite aggressive medical therapy, the patient died 10 days after admission. Postmortem examination disclosed severe, bilateral confluent bronchopneumonia, with numerous septated branching hyphae consistent with Aspergillus species fungal organisms that involved the pulmonary parenchyma and tracheobronchial tree. Although the small and large bowels were only mildly congested, the entire gastric mucosa was covered with a 1.5-cm-thick pseudomembrane that contained numerous Aspergillus organisms. Our report represents the first description, to our knowledge, of a diffuse inflammatory pseudomembrane in the stomach, a complication that to date has only been associated with small and large bowel involvement.
Pulmonary Vasculopathy in Idiopathic Spontaneous Pneumothorax in Young Subjects
Authors: Cyr Pamela V. , Vincic Lydia , Kay J. Michael
Published: January 2021

Background.—We have encountered instances where young subjects with idiopathic spontaneous pneumothorax have been needlessly referred for investigation of pulmonary hypertension because surgical pathologists have misinterpreted the significance of medial hypertrophy and intimal fibrosis of muscular pulmonary arteries in lung resection specimens.

Methods.—We reviewed 20 cases of idiopathic spontaneous pneumothorax and determined the prevalence and severity of medial and intimal lesions in the pulmonary arteries and pulmonary veins. We correlated the vascular changes with inflammation and fibrosis in the lung.

Results.—Pulmonary artery medial hypertrophy was seen in 15% of cases, pulmonary artery intimal fibrosis in 90% of cases, and pulmonary vein intimal fibrosis in 80% of cases. In 95% of cases, the lung showed some fibrosis and chronic inflammation. There was a significant positive correlation between pulmonary artery medial thickness and lung fibrosis and inflammation scores.

Conclusions.—Pulmonary artery medial hypertrophy and intimal fibrosis of pulmonary arteries and pulmonary veins are commonly seen in resected lung tissue from patients with idiopathic spontaneous pneumothorax. The vascular lesions are probably secondary to chronic inflammation and fibrosis in the adjacent lung. They are not clinically significant and do not represent hypertensive pulmonary vascular disease.
Diagnostic Value of Immunocytochemistry in Leptomeningeal Tumor Dissemination
Authors: Thomas Jean E. , Falls Evelyn , Velasco Manuel E. , Zaher Aiman
Published: January 2021

Differentiating chronic aseptic meningitis from leptomeningeal carcinomatosis or gliomatosis can be difficult, particularly when the differentiation is based solely on routine cytologic examination. The diagnosis of cerebrospinal fluid tumor dissemination in at-risk patients requires cytologic examination of cerebrospinal fluid and radiography of the leptomeninges. Routine cytologic examination alone has proven less than desirable, in most instances providing confirmation in as little as 50% of cases in the first lumbar puncture. This percentage increases to 85% to 90% after multiple lumbar punctures. We retrospectively reviewed 2 cases of leptomeningeal dissemination (one gliomatosis, the other carcinomatosis) with initial false-negative test results. However, after further examination of the cerebrospinal fluid by selected battery of immunocytochemical stains, both cases were identified as positive for malignancy (ie, false negatives). Immunocytochemistry can be useful in distinguishing chronic aseptic meningitis from leptomeningeal carcinomatosis or gliomatosis in patients at risk or when abnormal cells are seen on routine cerebrospinal fluid cytologic examination.
Coexisting Thymic and Gastric Lymphomas of Mucosa-Associated Lymphoid Tissues in a Patient With Sjögren Syndrome
Authors: Nagasaka Tetusuro , Lai Raymond , Harada Tomoko , Chen Yuan-Yuan , Chen Wen-Gang , Arber Daniel A. , Weiss Lawrence M.
Published: January 2021

Lymphomas of mucosa-associated lymphoid tissues (MALTomas) arising from the thymus are extremely rare. In this case report, we describe a 36-year-old woman with an 11-year history of Sjögren syndrome who was found to have a thymic MALToma coexisting with a gastric MALToma. Both tumors shared similar histologic features, showing clusters of centrocytic-like B cells, lymphoepithelial lesions, and prominent plasmacytic differentiation. They also showed the following identical immunohistochemical features: CD20+, IgA/λ+, CD5−, and CD43−. Molecular studies using polymerase chain reaction methods revealed monoclonal gene rearrangement of the immunoglobulin heavy chain in the gastric MALToma, but not in the thymic MALToma. The possible pathogenesis of this unusual case is discussed.
Recurrent Prostate Carcinoma Presenting as Omental Large Cell Carcinoma With Neuroendocrine Differentiation and Resulting in Bowel Obstruction
Authors: Wynn San San , Nagabundi Satyagnani , Koo Jaik , Chin Nena W.
Published: January 2021

Neuroendocrine differentiation in the neoplastic prostate varies from foci of adenocarcinoma showing immunoreactivity to the pure small cell carcinoma, which correlates with poor prognosis. Widely metastatic disease in unusual sites is reported for small cell carcinoma, and rarely is the serum prostate-specific antigen level elevated. We report a case of recurrent prostate adenocarcinoma presenting as bowel obstruction due to widespread metastatic disease in the omentum and peritoneum. The histopathology of the omental metastasis was that of a large cell neuroendocrine carcinoma, without evidence of an adenocarcinoma. The absence of a clinically evident second primary tumor, the concomitant elevated serum prostate-specific antigen level, and the positive tissue immunoreactivities to prostatic markers all supported the prostatic origin of the omental tumor. Review of the importance of prostatic neuroendocrine differentiation and its unusual metastatic patterns is presented.
Identification of Female Cells in Postcoital Penile Swabs Using Fluorescence In Situ Hybridization
Authors: Collins Kim A. , Cina Stephen J. , Pettenati Mark J. , Fitts Matthew
Published: January 2021

Traditionally, the finding of semen, that is, spermatozoa and acid phosphatase, in cervicovaginal specimens has been considered the laboratory evidence needed to prove recent sexual contact. Recent research with fluorescence in situ hybridization (FISH) has shown that in the absence of semen, male epithelial and inflammatory cells can be found within the female genital tract. A striking paucity of literature exists pertaining to the examination of the penis of an alleged assailant for potential evidence indicative of sexual assault. The current study uses FISH to analyzepostcoital swabs of the penis for such laboratory evidence.

A male and female volunteer couple consented to participate in this study. Following coitus, the male partner presented to one of the investigators for penile swabbing. Swabs were taken at varying postcoital intervals (1–24 hours) subsequent to 10 coital episodes. The male participant was instructed not to shower following coitus, but to otherwise go about daily activities until specimen collection. To obtain each sample, 4 sterile cotton-tipped applicators were slightly moistened in sterile saline and swabbed along the length of the penile shaft and around the base of the penis. From the swabs, 3 air-dried slides were prepared, coded, and blinded. As controls, swabs were taken from the buccal surfaces of both volunteers. Multicolor FISH was performed using dual X- and Y-chromosome probes, and slides were counterstained with 4′-6-diamidino-2-phenylindole (DAPI). Cells were easily visualized under a fluorescent microscope, but only cells with 2 nonoverlapping fluorescent signals were counted. Fluorescence in situ hybridization is highly sensitive and specific, and the dual probes easily distinguished between male and female cells. Female cells were identified on smears from every penile swab over the entire 1- to 24-hour postcoital interval. The FISH technique, previously successful in identifying male cells within the female genital tract, may also be employed on penile swabs. Once the presence of female cells is confirmed by FISH, the identity of the female can be confirmed by DNA analysis. Potentially, with such current molecular analyses, both the assailant and the victim can be positively identified.
Isolation and Identification of Male and Female DNA on a Postcoital Condom
Authors: Cina Stephen J. , Collins Kim A. , Fitts Matthew , Pettenati Mark J.
Published: January 2021

Background.—Identification of male perpetrators of sexual assault may be made from cells and fluids recovered from postcoital condoms. To date, the focus has been on identifying the person who had worn the condom.

Objective.—To describe a method for scientifically identifying both the male and female participants in a sex act by employing polymerase chain reaction–based technology on swabs taken from the internal and external surfaces of a condom. Fluorescence in situ hybridization may be used to screen for the presence of female cells on a condom.

Methods.—Swabs were taken from the internal and external surfaces of a condom 8 hours postcoitus. DNA was isolated from each swab through standard organic extraction. Extracted DNA was amplified for 8 different genetic loci using the Promega PowerPlex kit and the sex identification amelogenin marker. Amplified samples were electrophoresed on precast sequencing gels and analyzed fluorescently using a Hitachi FMBIO 2 fluorescent scanner and software. Each DNA sample obtained from the condom was compared with male and female buccal controls. At the time of collection, air-dried slides were prepared from the swabs for subsequent multicolor fluorescence in situ hybridization using dual X- and Y-chromosome probes with 4′-6-diamidino-2-phenylindole (DAPI) counterstaining.

Results.—A pure sample of female DNA was isolated from the external surface of the condom as determined by exclusive amplification of the X-chromosome–specific 212-base pair amelogenin marker. Swabs taken from the internal surface yielded DNA originating from the male participant. Identification was conclusive at 8 of 8 genetic loci. Fluorescence in situ hybridization identified pure populations of male epithelial cells from the internal surface of the condom and female cells from the external surface.

Conclusions.—Cells shed from a female during sexual intercourse can be retrieved from the external surface of a condom following sexual intercourse. Fluorescence in situ hybridization can be used to screen for the presence of female cells, and positive identification of the female sexual partner can then be made using polymerase chain reaction–based methods. We suggest that swabs taken from both surfaces of a condom used during sexual assault may be used to provide information that will definitively link the victim to the suspect.