bluuebunny/crossref_metadata_2025 huggingface dataset:
HAM56-Immunoreactive Macrophages in Untreated Infiltrating Gliomas
Authors: Cummings Thomas J. , Hulette Christine M. , Bigner Sandra H. , Riggins Gregory J. , McLendon Roger E.
Published: January 2021

Context.—Classic diagnostic neuropathologic teachings have cautioned against making the diagnosis of neoplasia in the presence of a macrophage population. The knowledge of macrophage distribution should prove useful when confronted with an infiltrating glioma containing macrophages.

Objective.—To identify macrophages in untreated, infiltrating gliomas using the monoclonal antibody HAM56, and to confirm their presence in an untreated glioblastoma multiforme (GBM) with the serial analysis of gene expression (SAGE) method.

Methods.—We evaluated the presence of macrophages in 16 cases of untreated, supratentorial infiltrating gliomas with the macrophage monoclonal antibody HAM56. We performed SAGE for one case of GBM and for normal brain tissue.

Results.—In World Health Organization (WHO) grade II well-differentiated astrocytoma and oligodendroglioma, HAM56 reactivity was noted only in endothelial cells, and unequivocal macrophages were not identified. In WHO grade III anaplastic astrocytoma and anaplastic oligodendroglioma, rare HAM56-positive macrophages were noted in solid areas of tumor. In WHO grade IV GBM, HAM56-positive macrophages were identified in areas of solid tumor (mean labeling index, 8.6%). In all cases of GBM, nonquantitated HAM56-positive macrophages were identified in foci of pseudopalisading cells abutting necrosis and in foci of microvascular proliferations. In none of the cases were granulomas or microglial nodules found, and there was no prior history of surgical intervention, radiation therapy, chemotherapy, or head trauma in these cases. By SAGE, the macrophage-related proteins osteopontin and macrophage-capping protein were overexpressed 12-fold and eightfold, respectively, in one untreated GBM compared with normal brain tissue. In this case, numerous HAM56-positive macrophages (labeling index, 24.5%) were present in the solid portion of tumor, and abundant nonquantified macrophages were identified in foci of pseudopalisading cells abutting necrosis and in foci of microvascular proliferations.

Conclusions.—This study confirms the utility of the monoclonal antibody HAM56 in identifying macrophages within untreated infiltrating gliomas. The overexpression of macrophage-related proteins in one case of GBM as detected by SAGE signifies that macrophages may be present in untreated GBMs.
Bilateral Renal Oncocytosis With Renal Failure
Authors: Leroy Xavier , Lemaitre Laurent , De La Taille Alexandre , Hazzan Marc , Delepaul Bruno , Couturier Jerome , Gosselin Bernard
Published: January 2021

Oncocytosis is a term recently used to describe diffuse renal involvement by numerous oncocytic nodules. We report herein a case of a 53-year-old man with end-stage renal disease requiring hemodialysis. His kidneys were involved by numerous tumors. Histologic examination revealed more than 100 oncocytomas and an associated papillary renal cell carcinoma in the right kidney.
True Hemangiopericytoma of the Nasal Cavity
Authors: Watanabe Kazuo , Saito Atsuko , Suzuki Masahiro , Yamanobe Shu , Suzuki Toshimitsu
Published: January 2021

Two cases of nasal tumors with pericytic myoid differentiation are reported. The tumors occurred in a 77-year-old woman and a 60-year-old man as polypoid lesions covered by normal mucosa. Histologically, the tumors were composed of uniform short spindle or stellate cells with indistinct cell borders arranged in narrow and short fascicles. Numerous blood vessels of various sizes were common in both cases. The tumor cells of both cases stained intensely with anti-vimentin and anti-actin antibodies, but not with anti-desmin, CD34, or anti–high-molecular-weight caldesmon antibodies. Ultrastructural examination revealed well-developed actin thin filaments with dense bodies, subplasmalemmal plaques, intercellular junctions, and irregular discontinuous basement membranes. These histopathologic features suggest true pericytic differentiation of the tumors (true hemangiopericytoma), unlike soft tissue–type hemangiopericytoma. Generally, sinonasal hemangiopericytomas are subdivided into soft tissue–type hemangiopericytomas and true hemangiopericytomas identical to the cases presented here. Soft tissue–type hemangiopericytomas are frequently highly aggressive, whereas true hemangiopericytomas show localized benign behavior. Sinonasal true hemangiopericytomas should be strictly differentiated from soft tissue–type hemangiopericytomas.
Fluorescence In Situ Hybridization and Immunohistochemical Assays for HER-2/neu Status Determination
Authors: Onody Peter , Bertrand Françoise , Muzeau Françoise , Bièche Ivan , Lidereau Rosette
Published: January 2021

Background.—HER-2/neu (ERBB2) gene amplification and/or overexpression is a major event in human breast tumorigenesis. HER-2/neu gene alterations have been the most frequently assessed prognostic factors during the last 10 years in breast cancer and have recently emerged as a management decision tool and a therapeutic target. There is still controversy over the best method to determine whether a tumor is HER-2/neu positive. Because of the increasing demand for HER-2/neu gene status determination in clinical practice, we compared HER-2/neu gene alterations at the DNA level (gene amplification) and the protein level (overexpression) in a panel of patients with lymph node–negative breast cancer who had received local radiotherapy alone, with no adjuvant therapy.

Methods.—We tested 100 excised lymph node–negative breast tumors, using fluorescence in situ hybridization (FISH) with a biotinylated HER-2/neu DNA probe and immunohistochemical assays (IHC) with 2 different antibodies.

Results.—The FISH frequency of HER-2/neu gene amplification was 15%, and the IHC frequency of overexpression was 21%.

Conclusion.—Although HER-2/neu amplification by FISH and HER-2/neu overexpression by IHC correlated well in this panel of lymph node–negative breast carcinomas, there were a number of discordant cases, pointing to the important need for determining HER-2/neu alteration for the future management of HER-2/neu–based clinical applications.
Dural Metastases
Authors: Kleinschmidt-DeMasters B. K.
Published: January 2021

Background.—Metastases to dura constitute one of the least frequent and least studied patterns of neoplastic spread to the craniospinal axis. Older reports cited breast cancer as accounting for the largest number of dural metastases, often as a manifestation of end-stage disease. Since the early 1980s we have noted an increasing number and diversity of cancer types in patients with dural metastases in our surgical and autopsy neuropathology experience. Some surgical patients have experienced prolonged postoperative survival.

Methods.—Review of autopsy records from 1982 to 1999 and surgical pathology records from 1990 to 2000 at a large university teaching hospital, including consultation files.

Results.—Dural metastases removed at surgery (n = 33) were usually single, cranial, subdural lesions; coexistence with brain parenchymal or skull metastases varied according to tumor type. Unusual tumor types included carcinomas of colon, endometrium, cervix, and stomach. One well-documented patient developed postsurgical implantation metastases, and 2 patients had co-associated acute subdural hematomas. Surgical patients showed widely varying postoperative survival times, but in several of these patients survival times were in excess of 2 years. Dural metastases seen at autopsy (n = 27) could also be solitary and nodular, but more examples were extensive, diffuse, and both subdural and epidural in location. The expected cases of breast cancer (n = 5) occurred, but more examples of prostate cancer (n = 7) or unusual malignant neoplasms (cervical = 3, laryngeal = 1, gallbladder = 1, Ewing sarcoma = 1, intravascular lymphomatosis = 1, ocular melanoma = 1) were identified.

Conclusions.—This combined surgical and autopsy series shows a different distribution of tumor types causing dural metastases than older series. Postoperative outcome may be favorable in select, surgically treated patients.
Cytokeratin 7 and Cytokeratin 20 in Primary Urinary Bladder Carcinoma and Matched Lymph Node Metastasis
Authors: Jiang Jiazhong , Ulbright Thomas M. , Younger Cheryl , Sanchez Katya , Bostwick David G. , Koch Michael O. , Eble John N. , Cheng Liang
Published: January 2021

Background.—Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits.

Objective.—To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis.

Design.—We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases.

Results.—In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases.

Conclusions.—CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.
Dura Mater Involvement in Ochronosis (Alkaptonuria)
Authors: Liu Wendy , Prayson Richard A.
Published: January 2021

Clinical manifestations of alkaptonuria have been well described and are most commonly characterized by ochronosis or pigmentation of connective tissue. Sites most commonly involved in ochronosis include joints, heart, skin, and kidney. We describe a 66-year-old woman with a history of alkaptonuria who had widespread ochronosis. The dura mater showed extensive pigment deposition, which was evident both grossly and microscopically at autopsy. To our knowledge, description of dura mater involvement by ochronosis has not been previously reported in the literature.
Decreasing Incidence of Sudden Death Due to Undiagnosed Primary Central Nervous System Tumors
Authors: Eberhart Charles G. , Morrison Alan , Gyure Kymberly A. , Frazier James , Smialek John E. , Troncoso Juan C.
Published: January 2021

Context.—Although most fatal brain tumors are diagnosed well before a patient's death, occasionally medical examiners and coroners encounter cases in which the presence of a primary tumor of the central nervous system (CNS) was not suspected prior to death. Analysis of such cases can shed light on specific pitfalls hindering the diagnosis of brain tumors. In addition, by analyzing the incidence of these cases in a large autopsy series, one can draw conclusions about the evolving effectiveness of medical diagnosis.

Objective.—To determine the incidence of deaths due to undiagnosed primary CNS tumors in the era of advanced neuroimaging techniques.

Design.—Records from forensic autopsies performed during a 20-year period (1980–1999) at the Office of the Chief Medical Examiner of the State of Maryland were reviewed to identify cases in which death was caused by primary CNS tumors undiagnosed prior to the patient's death.

Results.—We present 11 cases of undiagnosed primary CNS tumors resulting in sudden death that were identified among 54 873 forensic autopsies. Sudden deaths due to undiagnosed CNS neoplasms account for a significantly lower percentage of cases in our study (0.02%) than in similar series reported prior to 1980 (≥0.16%).

Conclusions.—We hypothesize that improvements in imaging techniques, notably the introduction of computed tomography and magnetic resonance imaging, have resulted in increased early detection of CNS neoplasms. However, vague or short-term symptoms and limited health care access can dissuade patients from seeking medical attention and result in failure to diagnose these tumors correctly.
CD30 Expression in Follicular Lymphoma
Authors: Gardner Laura J. , Polski Jacek M. , Evans H. Lance , Perkins Sherrie L. , Dunphy Cherie H.
Published: January 2021

Context.—CD30+ anaplastic large cell lymphomas were originally described as being of T-cell, null cell, and B-cell origin. CD30, however, is not a specific marker of anaplastic large cell lymphoma and has been found to be expressed in reactive as well as neoplastic populations as a probable activation marker. In addition, CD30+ cells have also been described in both diffuse large B-cell and follicular lymphomas (FLs), resembling the pattern seen in reactive tonsils and lymph nodes.

Objective.—We report an index case of FL with CD30 expression, which on initial touch preparations and flow cytometric immunophenotyping revealed a prominent population of CD30+ cells with marked cellular pleomorphism (anaplasia) in a background of typical FL. Immunohistochemistry of the paraffin section for CD30 in our index case confirmed unequivocal CD30+ pleomorphic cells in the malignant nodules in occasional clusters. This case prompted a study of additional cases of FL for pattern of immunoreactivity with CD30 on paraffin sections.

Design.—Twenty-two additional cases of FL (grades 1–3) were retrieved for CD30 immunoperoxidase staining as in the index case.

Results.—This study demonstrated 32% of the additional cases of FL had definitive CD30+, large, pleomorphic malignant cells by paraffin immunohistochemistry. In 2 cases (9%), the pattern of immunoreactivity with CD30 showed clustering and variable staining of large cells, as our index case.

Conclusion.—This study underscores the morphologic and immunophenotypic spectrum of FL that includes CD30 staining and cellular pleomorphism.
The Histopathology of 103 Consecutive Colonoscopy Biopsies From 82 Symptomatic Patients With Acquired Immunodeficiency Syndrome
Authors: Orenstein Jan Marc , Dieterich Douglas T.
Published: January 2021

Objective.—To compare the primary diagnoses assigned by general surgical pathologists on a series of 103 consecutive colon biopsies from individuals infected with human immunodeficiency virus (HIV) with diagnoses rendered by a pathologist with extensive experience in gastrointestinal pathology in HIV/acquired immunodeficiency syndrome.

Design.—New sections were cut from paraffin blocks of 103 consecutive colon biopsies taken during colonoscopies of 82 different HIV-infected patients; all new sections were stained with hematoxylin-eosin. These individuals either had negative stool studies or had failed to respond to therapy and had chronic large bowel symptoms, such as frequent small volume–type diarrhea, tenesmus, and/or bright red blood per rectum. Immunohistochemistry for cytomegalovirus (CMV) was performed on 18 of 22 specimens originally diagnosed with CMV colitis.

Results.—The initial study yielded 70 (68%) negative or nonspecific diagnoses, 22 (21%) cases of CMV colitis, 5 (5%) Cryptosporidium diagnoses, 2 cases each of adenomatous polyps and Kaposi sarcoma, and 1 case each of spirochetosis and squamous cell carcinoma of the anorectum. Review of the recuts yielded 64 (62%) negative or nonspecific diagnoses, 12 (12%) new adenovirus infections (3 combined with CMV), and 11 (11%) lone CMV infections. Three attaching and effacing bacterial infections were diagnosed, 1 with adenovirus coinfection. A total of 4 spirochetosis cases were found on review. Seven (7%) of the biopsies showed at least 1 coinfection. Nine biopsies had features suggestive of inflammatory bowel disease.

Conclusions.—Colonoscopy with biopsy after negative stool studies or failure to respond to therapy yielded a high proportion of negative or nonspecific diagnoses. Adenovirus and enteropathogenic bacterial infections had been totally overlooked on initial examination. It takes particular experience to evaluate gastrointestinal biopsies from HIV-infected patients.
The Small Blue Cell Dilemma Associated With Tamoxifen Therapy
Authors: Yang Yi Jun , Trapkin Linda K. , Demoski Roberta K. , Bellerdine Jeannette , Powers Celeste N.
Published: January 2021

Context.—Several endometrial diseases, such as endometrial hyperplasia, endometrial carcinoma, and endometrial polyps, have been reported to be associated with tamoxifen administration. We recently observed a high incidence of distinctive small blue cells in Papanicolaou tests of women who had received tamoxifen treatment for breast carcinoma.

Objectives.—To define the characteristics of these small blue cells, to identify the patient population in which they are found, and to determine the clinical significance and possible etiology of these findings.

Design.—A total of 154 Papanicolaou tests from 60 patients with a clinical history of tamoxifen therapy were reviewed retrospectively.

Results.—Small blue cells were found in 40% of Papanicolaou tests from patients who received tamoxifen therapy. Patients with small blue cells in their Papanicolaou tests were an average of 9 years older at the time tamoxifen therapy was initiated than those without. Among the available follow-up surgical biopsies, no malignant diagnoses were made.

Conclusions.—We conclude that these distinctive small blue cells are found more frequently in older patients and most probably represent proliferative reserve cells of cervical/vaginal epithelium resulting from the estrogenic agonist effect of tamoxifen. More importantly, they are nonneoplastic in nature.
Major Pancreatic Resections for Chronic Pancreatitis
Authors: Proca Daniela M. , Ellison E. Christopher , Hibbert Dan , Frankel Wendy L.
Published: January 2021

Objective.—Indications for major pancreatic resections have been expanded to include complicated chronic pancreatitis (CP). We assessed clinical findings and outcomes and evaluated histology in patients who had major pancreatic resections for CP. We also determined if histologic findings were associated with persistent postoperative pain.

Design.—We reviewed charts and slides from 44 patients who underwent major pancreatic resections for CP between 1989 and 1999.

Results.—The etiology for disease included alcohol (n = 15), hereditary (n = 5), idiopathic (n = 6), pancreas divisum (n = 3), stricture (n = 2), trauma (n = 2), systemic lupus erythematosus (n = 1), and unknown (n = 10). Patients included 20 men and 24 women; ages ranged from 22 to 76 years. Perioperative mortality and morbidity were 0% and 4.5%, respectively. Persistent pain was present in 25 (57%) of the 44 patients, and pain was encountered more frequently in patients with alcoholic pancreatitis (67%) versus other etiologies (52%), and in those who underwent Whipple/Beger or total resections (68%) versus distal or subtotal pancreatectomy (42%). Metaplastic changes were present in 14 cases, and ductal atypia was seen in 9 cases. No malignancies were found. Acinar necrosis and acute inflammation were seen more often in patients with persistent pain than in those who were pain free (P = .081).

Conclusions.—Major pancreatic resection for CP can be performed with low morbidity and mortality. This procedure relieves pain in nearly half the patients. There is a wide spectrum of histopathologic changes seen in CP, including ductal atypia and metaplastic changes. Acute exacerbations of CP identified histologically at the time of surgery and alcohol as etiology for CP may be associated more frequently with intractable pain.
Pagetoid Dyskeratosis Is a Frequent Incidental Finding in Hemorrhoidal Disease
Authors: Val-Bernal J. Fernando , Pinto Jesús
Published: January 2021

Background.—Pagetoid dyskeratosis is considered a selective keratinocytic response in which a small part of the normal population of keratinocytes is induced to proliferate. Pagetoid dyskeratosis has been found incidentally in the squamous epithelium of the skin in various locations and in the ectocervix in uterine prolapse. In cases in which these pale cells are conspicuous, there is a hazard of overdiagnosis. It has been suggested that friction is the most probable inductor of the lesion. To the best of our knowledge, pagetoid cells have not been reported in surgically resected hemorrhoids.

Objective and Design.—We here describe the location of pagetoid dyskeratosis in the squamous epithelium of hemorrhoids and the incidence of this lesion in a group of 100 unselected patients surgically treated for hemorrhoidal disease. In addition to the conventional histologic method, special staining procedures and an immunohistochemical study of cytokeratins were performed in selected cases.

Results.—Pagetoid dyskeratosis was found in 68 cases (68%) and was a prominent finding in 22 cases (22%). The cells of pagetoid dyskeratosis were strongly positive for high–molecular weight cytokeratin. These cells showed an immunohistochemical profile that was different from that of the surrounding squamous cells and indicative of premature keratinization.

Conclusions.—In hemorrhoidal disease, the cushions are susceptible to trauma as a result of prolapse. In this setting, friction may be the stimulus for the appearance of pagetoid dyskeratotic cells. These cells must be distinguished from the artifactual clear cells of the squamous epithelium, glycogen-rich cells, and koilocytes. The lesion must also be distinguished from extramammary Paget disease, pagetoid spread of carcinoma cells, pagetoid Bowen disease, and pagetoid melanoma. Pathologists should be familiar with the histologic features of pagetoid dyskeratosis in hemorrhoidectomy specimens to avoid misdiagnosis. Routine histologic study is usually adequate for recognizing this lesion.
Evaluation of Bone Marrow Specimens With Acute Myelogenous Leukemia for CD34, CD15, CD117, and Myeloperoxidase
Authors: Dunphy Cherie H. , Polski Jacek M. , Evans H. Lance , Gardner Laura J.
Published: January 2021

Context.—Immunophenotyping of bone marrow (BM) specimens with acute myelogenous leukemia (AML) may be performed by flow cytometric (FC) or immunohistochemical (IH) techniques. Some markers (CD34, CD15, and CD117) are available for both techniques. Myeloperoxidase (MPO) analysis may be performed by enzyme cytochemical (EC) or IH techniques.

Objective.—To determine the reliability of these markers and MPO by these techniques, we designed a study to compare the results of analyses of these markers and MPO by FC (CD34, CD15, and CD117), EC (MPO), and IH (CD34, CD15, CD117, and MPO) techniques.

Materials and Methods.—Twenty-nine AMLs formed the basis of the study. These AMLs all had been immunophenotyped previously by FC analysis; 27 also had had EC analysis performed. Of the AMLs, 29 had BM core biopsies and 26 had BM clots that could be evaluated. The paraffin blocks of the 29 BM core biopsies and 26 BM clots were stained for CD34, CD117, MPO, and CD15. These results were compared with results by FC analysis (CD34, CD15, and CD117) and EC analysis (MPO).

Results.—Immunodetection of CD34 expression in AML had a similar sensitivity by FC and IH techniques. Immunodetection of CD15 and CD117 had a higher sensitivity by FC analysis than by IH analysis. Detection of MPO by IH analysis was more sensitive than by EC analysis. There was no correlation of French-American-British (FAB) subtype of AML with CD34 or CD117 expression. Expression of CD15 was associated with AMLs with a monocytic component. Myeloperoxidase reactivity by IH analysis was observed in AMLs originally FAB subtyped as M0.

Conclusions.—CD34 can be equally detected by FC and IH techniques. CD15 and CD117 are better detected by FC analysis and MPO is better detected by IH analysis.
Primary Plasmacytoma of the Breast
Authors: De Chiara Annarosaria , Losito Simona , Terracciano Luigi , Di Giacomo Raimondo , Iaccarino Giancarla , Rubolotta Maria R.
Published: January 2021

We describe a solitary extramedullary plasmacytoma of the breast in a 37-year-old woman. No other involvement was detected in the bone marrow or in any other site during a 15-month follow-up period. Extramedullary plasmacytomas of the breast are extremely rare, especially those that are not associated with multiple myeloma. We review the histologic features of the previously reported cases with an emphasis on differential diagnosis and the difficulties encountered in arriving at the correct diagnosis in frozen sections.
Adult Extrarenal Wilms Tumor Occurring in the Uterus
Authors: Muc Ronald S. , Grayson Wayne , Grobbelaar Johannes J.
Published: January 2021

Five previous cases of extrarenal Wilms tumor (EWT) occurring in the uterus have been reported. The oldest patient was 22 years. We report a case of uterine EWT occurring in a 42-year-old woman. Histologically, there was typical triphasic differentiation, including epithelial, blastemal, and mesenchymal elements. The important differential diagnosis in this age group, the malignant mixed mullerian tumor, is excluded by the absence of glomeruloid structures and primitive tubules. The exact histogenesis of EWT is unknown but most likely relates to the presence of nephrogenic rests occurring in the female genital tract.
Six-Year Trends in Productivity and Utilization of 73 Clinical Laboratories
Authors: Valenstein Paul N. , Praestgaard Amy H. , Lepoff Ronald B.
Published: January 2021

Objectives.—To describe longitudinal trends in the efficiency, labor productivity, and utilization of clinical laboratories in the United States.

Methods.—Financial and activity data were prospectively collected from 73 clinical laboratories continuously enrolled in the College of American Pathologists Laboratory Management Index Program from 1994 through 1999. Each laboratory reported quarterly on its costs, labor inputs, and test activity using uniform data definitions.

Results.—During the 6-year study period, there was a significant increase in laboratory labor productivity (2.1% more tests/full-time equivalent/y; P < .001). Productivity increases were offset by increasing labor expense (1.5%/full-time equivalent/y; P < .001), consumable expense (1.7%/on-site test/y; P = .005), and blood expense, which comprised more than 10% of laboratory expenses by 1999 (4.4% increase/y; P < .001). As a result, overall expense per test showed no significant change in non–inflation-adjusted dollars. Reference laboratory expense per test did not change significantly during the study period; the proportion of tests sent to reference laboratories grew slightly (0.06% increase/y; P < .001). Test volume of the median laboratory grew by 5442 tests per year (2.3% annual increase; P < .001), while the proportion of testing from inpatients declined by 1.7% per year (P < .001). Inpatient test utilization declined on a discharge basis (annual decline of 1.2 tests/inpatient discharge; P < .001) and on a per diem basis (annual decline of 0.08 tests/inpatient day; P = .002). Inpatient laboratory expense declined on a discharge basis (annual decline of $2.40 or 1.3% per discharge; P < .001), but did not change significantly per inpatient day. Most of the reduction in the expense per discharge occurred during 1994–1996.

Conclusions.—Between 1994 and 1999, clinical laboratories in the United States experienced significant changes in the cost of operations, utilization, and labor productivity. Laboratory administrators who compare local institutional performance with that of peers are advised to use current or forward-trended peer data. Quarter-to-quarter improvement in many measures of laboratory financial activity may not signal a superior operation, as performance of the whole industry appears to be improving.
Conserved Genetic Findings in Metastatic Bladder Cancer
Authors: Cheng Liang , Bostwick David G. , Li Guang , Zhang Shaobo , Vortmeyer Alexander O. , Zhuang Zhengping
Published: January 2021

Context.—Molecular analysis of microsatellite alterations of biologically distinct tumor cell subpopulations from the same patient may aid in the determination of tumor origin and further our understanding of the genetic basis of cancer progression.

Design.—The authors examined the pattern of allelic loss with polymorphic microsatellite markers on chromosome 9p21 (D9S161, D9S171, IFNA), regions of putative tumor suppressor gene p16, and on chromosome 17p13 (TP53), the p53 locus, in matched primary and metastatic bladder cancers from 9 patients. All patients underwent cystectomy for bladder cancer and had regional lymph node metastases at the time of surgery. Genomic DNA was prepared from primary cancers and matched synchronous lymph node metastases using a microdissection method.

Results.—The overall frequency of allelic loss was 78% in primary cancer and 89% in paired metastatic cancer. The frequency of allelic loss in the primary cancer was 86% with D9S161, 67% with D9S171, 71% with IFNA, and 80% with TP53. The frequency of allelic loss in matched metastatic cancer was 100% with D9S161, 62% with D9S171, 71% with IFNA, and 80% with TP53. An identical pattern of allelic imbalance (allelic loss or retention) at multiple DNA loci was observed in matched primary and metastatic carcinoma in 8 (88%) cases. One case showed allelic loss in the metastasis, but not in the primary cancer.

Conclusions.—The pattern of allelic loss at chromosome 9p21 (p16) and 17p13 (p53) was generally maintained during cancer progression to metastasis, and identical allelic loss in primary cancer was conserved in paired metastatic carcinoma. These data suggest that these genetic changes may be useful in establishing a diagnosis and determining tumor origins in difficult cases.
Three-Dimensional Organization of the Hepatic Microvasculature in Hereditary Hemorrhagic Telangiectasia
Authors: Sawabe Motoji , Arai Tomio , Esaki Yukiyoshi , Tsuru Masanobu , Fukazawa Toshio , Takubo Kaiyo
Published: January 2021

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic fibrovascular dysplasia. Although hepatic vascular shunts are often observed in HHT, the responsible pathological mechanism is unknown. This issue was addressed by performing a 3-dimensional reconstruction study of the hepatic microvasculature of an HHT-involved liver in a 79-year-old woman. Clinical observation revealed high-output congestive heart failure and hepatic encephalopathy due to arteriovenous and portovenous shunts, respectively. Angiography revealed tortuous dilation of hepatic arterial branches and intrahepatic arteriovenous shunts. The 3-dimensional analysis of the autopsy liver revealed focal sinusoidal ectasia, arteriovenous shunts through abnormal direct communications between arterioles and ectatic sinusoids, and portovenous shunts due to frequent and large communications between portal veins and ectatic sinusoids. Type 1 HHT was suggested by the lack of endoglin immunoreactivity in the liver. The 3-dimensional reconstruction study of hepatic microvasculature was successful in identifying the pathological changes responsible for the intrahepatic shunts in HHT.
Renal Cell Carcinoma With Intravascular Lymphomatosis
Authors: Wang Beverly Y. , Strauchen James A. , Rabinowitz David , Tillem Steven M. , Unger Pamela D.
Published: January 2021

We report the case of a 77-year-old white woman who presented with a left breast mass, lethargy, and weight loss. Pelvic computed tomographic scan revealed a 9.5-cm mass in the right kidney. Surgical pathology demonstrated a diffuse large B-cell lymphoma of the subcutaneous tissue of the breast and renal cell carcinoma with concurrent extensive intravascular lymphomatosis. Systemic dissemination of malignant lymphoma to a concurrent visceral primary neoplasm is rare. To the best of our knowledge, this is the first case illustrating a renal cell carcinoma collision with intravascular lymphomatosis.
Association of Primary Pleural Effusion Lymphoma of T-Cell Origin and Human Herpesvirus 8 in a Human Immunodeficiency Virus–Seronegative Man
Authors: Lechapt-Zalcman Emmanuèle , Challine Dominique , Delfau-Larue Marie-Hélène , Haioun Corinne , Desvaux Dominique , Gaulard Philippe
Published: January 2021

We describe a case of an 87-year-old human immunodeficiency virus (HIV)–negative man who developed a primary pleural lymphoma without any identifiable tumor mass associated with human herpesvirus 8 (HHV-8) infection. A large T-cell lymphoma was diagnosed based on morphologic, immunophenotypic, and molecular findings. The HHV-8 DNA sequences were detected using specific polymerase chain reaction amplification in the lymphomatous effusion. Study of the patient's serum confirmed the HHV-8 infection. This case report displays the characteristic features of HHV-8–related body cavity-based lymphoma/primary effusion lymphoma previously reported in HIV-seronegative patients, except that it is of T-cell origin. Whether this case may be included or not within the primary effusion lymphoma entity, the association of a pleural T-cell non-Hodgkin lymphoma with HHV-8 infection raises the question of the possible occurrence of T cells as the target of malignant transformation associated with HHV-8 infection.
Malignant Melanoma
Authors: Slominski Andrzej , Wortsman Jacobo , Carlson Andrew J. , Matsuoka Lois Y. , Balch Charles M. , Mihm Martin C.
Published: January 2021

Context.—The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic techniques and potential therapeutic approaches.

Objectives.—To present the most current concepts on the etiology and pathogenesis of melanoma and to introduce the recent diagnostic techniques and the potential therapeutic approaches.

Methods.—Data sources were reports on melanoma published in the English language literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola University Medical Center, and University of Tennessee Health Science Center.

Results.—Studies on melanoma containing chromosomal or genetic evaluation were selected for further analysis. Current clinical and pathologic categories with the reported genetic abnormalities were related to the latest information on pigment biology. The data extracted were used to develop a conceptual framework on the pathogenesis of melanoma; the generated model was then evaluated and used to suggest potential therapeutic approaches.

Conclusions.—(1) Melanoma is not genetically homogenous, and the existing differences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension, ulceration of primary tumor, and metastatic process, have profound prognostic and therapeutic implications. (2) Chromosomal aberrations and gene mutations are found in sporadic and familial melanomas; among the most important are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expression is associated with more aggressive behavior. (3) Melanoma cells possess a remarkable repertoire of biosynthetic capacities represented by the production of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products α-melanocyte-stimulating hormone and adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, but also as potential targets for melanoma therapy.
Immunohistochemical Analysis of Nuclear Versus Cytoplasmic Staining of WT1 in Malignant Mesotheliomas and Primary Pulmonary Adenocarcinomas
Authors: Foster Matthew R. , Johnson Joyce E. , Olson Sandy J. , Allred D. Craig
Published: January 2021

Context.—Previous studies have indicated certain immunohistochemical markers, including WT1, may be helpful in distinguishing adenocarcinomas from mesotheliomas, but to date there are no reliable, widely accepted, commercially available antibodies positive in mesotheliomas and negative in adenocarcinomas. We compared the nuclear and cytoplasmic staining patterns of WT1 in these 2 malignancies using a commercially available antibody and examined the expression of 2 other previously reported positive markers, calretinin and thrombomodulin.

Methods.—Sixty-seven mesotheliomas and 51 adenocarcinomas, all paraffin embedded, were retrieved from recent case files. The diagnosis of mesothelioma was based on typical clinical and morphologic features, as well as immunohistochemistry; electron microscopy had been performed on 16 cases. The diagnosis of adenocarcinoma was based on typical light microscopic findings and a positive stain for mucin. Commercially available antibodies to WT1, thrombomodulin, and calretinin were applied. Because of the conflict surrounding calretinin, 2 anticalretinin antibodies (from Chemicon Inc and Zymed Laboratories) were utilized.

Results.—Fifty of 67 mesotheliomas showed strong nuclear staining with WT1. No adenocarcinomas (0/51) showed nuclear staining. Twenty-three of 67 mesotheliomas were positive for thrombomodulin, and 35 of 67 mesotheliomas were positive for calretinin with the Chemicon antibody. Nine of 15 mesotheliomas were positive for calretinin with the Zymed antibody.

Conclusions.—Thrombomodulin and calretinin did not prove useful in discriminating between mesotheliomas and adenocarcinomas. The degree of positivity with calretinin may be dependent on the specific antibody utilized. Nuclear staining for WT1 is highly specific for mesothelioma and, in the appropriate clinical setting, can be a helpful adjunct in the distinction between adenocarcinomas and mesotheliomas.
Urothelial and Prostate Carcinoma Metastasizing to the Same Lymph Node
Authors: Overstreet Kerith , Haghighi Parviz
Published: January 2021

We report herein a case of a collision tumor composed of high-grade urothelial carcinoma and a Gleason grade 3+4 prostate adenocarcinoma metastasizing to the same lymph node. After the patient underwent cystoprostatectomy for known urothelial carcinoma, he was incidentally discovered to have a second primary prostate tumor. Lymph node examination revealed that one node appeared to have metastatic foci from both primary tumors. The presence of 2 tumor types colliding in the same lymph node was confirmed using immunohistochemical stains, including monoclonal carcinoembryonic antigen, prostate-specific antigen, prostatic acid phosphatase, cytokeratins 7 and 20, and CD57. We also stained both primary tumors with the same panel as an internal control. Although 2 similar collision tumors have been reported in the literature in the past, neither used a battery of immunohistochemical stains to definitively distinguish one tumor from the other. Herein, we review the literature on urothelial and prostate collision tumors and some of the special stains used to distinguish them.
Malignancies Arising in Oncocytic Schneiderian Papillomas
Authors: Maitra Anirban , Baskin Leland B. , Lee Edward L.
Published: January 2021

Oncocytic schneiderian papillomas (OSPs) are uncommon benign neoplasms that arise from the sinonasal schneiderian epithelium. Malignancies arising in OSPs are rare, and, to our knowledge, only 14 such instances have been reported in the medical literature. We report 2 additional cases—a small cell carcinoma and a sinonasal undifferentiated carcinoma arising in OSPs and presenting synchronously with the benign neoplasm. The potential for malignant transformation in OSPs is small, but warrants that these papillomas be completely excised to exclude a coexisting carcinoma.
Invasive Secretory (Juvenile) Carcinoma Arising in Ectopic Breast Tissue of the Axilla
Authors: Shin Sandra J. , Sheikh Farrukh S. , Allenby Patricia A. , Rosen Paul Peter
Published: January 2021

Mammary carcinoma arising in ectopic breast tissue is an uncommon occurrence. Most reported cases have involved ductal carcinoma, but other types, such as medullary, papillary, and lobular carcinomas, have been described. For pathologists, the diagnosis of mammary carcinoma arising in ectopic breast tissue can be difficult, especially in the axilla, where carcinoma of adnexal origin must be excluded. We describe a 46-year-old woman who developed invasive (juvenile) secretory carcinoma in ectopic right axillary breast tissue and micrometastatic carcinoma in an ipsilateral axillary lymph node. The carcinoma arose in a right axillary mass that had been present for 8 years, from which she had secreted fluid during prior breast-feeding. To our knowledge, this is the first report of secretory carcinoma arising in axillary breast tissue to be documented in the current literature.
Achondrogenesis Type IB
Authors: Corsi Alessandro , Riminucci Mara , Fisher Larry W. , Bianco Paolo
Published: January 2021

Achondrogenesis type IB is a lethal osteochondrodysplasia caused by mutations in the diastrophic dysplasia sulfate transporter gene. How these mutations lead to the skeletal phenotype is not known. Histology of plastic-embedded skeletal fetal achondrogenesis type IB samples suggested that interterritorial epiphyseal cartilage matrix was selectively missing. Cartilage was organized in “chondrons” separated by cleft spaces; chondrocyte seriation, longitudinal septa, and, in turn, mineralized cartilaginous septa were absent. Agenesis of interterritorial matrix as the key histologic change was confirmed by immunohistology using specific markers of territorial and interterritorial matrix. Biglycan-enriched territorial matrix was preserved; decorin-enriched interterritorial areas were absent, although immunostaining was observed within chondrocytes. Thus, in achondrogenesis type IB: (1) a complex derangement in cartilage matrix assembly lies downstream of the deficient sulfate transporter activity; (2) the severely impaired decorin deposition participates in the changes in matrix organization with lack of development of normal interterritorial matrix; and (3) this change determines the lack of the necessary structural substrate for proper endochondral bone formation and explains the severe skeletal phenotype.
Aortic and Mitral Fenfluramine-Phentermine Valvulopathy in 64 Patients Treated With Anorectic Agents
Authors: Volmar Keith E. , Hutchins Grover M.
Published: January 2021

Context.—Few published studies of the pathology of fenfluramine-phentermine (fen-phen) valvulopathy, described by Connolly and colleagues in 1997, have appeared.

Objectives.—To define temporal changes in the morphology of the stuck-on plaques and to determine whether the plaques progress or regress after cessation of fen-phen.

Methods.—The available clinical information and pathology material from 35 aortic valves (AVs) and 43 mitral valves (MVs) from 64 patients were reviewed.

Results.—The valves fell into 3 groups: 17 AVs and 28 MVs had fen-phen lesions only, 2 AVs and 7 MVs had fen-phen changes associated with other valve diseases, and 16 AVs and 8 MVs had no fen-phen changes. Fenfluramine-phentermine–attributable dysfunction was regurgitation in all instances. Typical plaques showed proliferation of myofibroblastic cells with myxoid stroma. Small vascular channels and slight lymphocytic accumulations were often present. Deeper parts of some plaques had dense fibroelastic tissue underlying typical plaque.

Conclusions.—Considerable individual variation in the time course of anorectic agent use and the severity of fen-phen valvulopathy was observed. Possible plaque regression could not be assessed from this study. The observations suggest that in some patients fen-phen–induced plaques may continue to have surface proliferation despite drug withdrawal.
Clear Cell Odontogenic Carcinoma
Authors: Li Tie-Jun , Yu Shi-Feng , Gao Yan , Wang En-Bo
Published: January 2021

Context.—Odontogenic tumor composed predominantly of clear cells is a rare neoplasm of the jaws that was initially designated as clear cell odontogenic tumor. Subsequent reports in the literature, however, all have indicated that this tumor exhibits an aggressive behavior characterized by infiltrative local growth, recurrence, or metastases.

Objective.—To ascertain the clinicomorphologic features and biologic behavior of this tumor group, we present 5 additional cases using the term clear cell odontogenic carcinoma.

Design.—Histologic and immunohistochemical examinations were performed on clear cell odontogenic carcinomas from 5 patients. Clinical and follow-up data were recorded, and the literature was reviewed.

Results.—The patients were 1 man and 4 women with an average age of 42.4 years at diagnosis. Three tumors occurred in the mandible and the other 2 in the maxilla. Four of the 5 cases occurred in the anterior or premolar areas of the jaws, appearing as poorly marginated radiolucencies. All cases consisted of islands and sheets of large clear cells and small basaloid cells with scanty eosinophilic cytoplasm, which were separated by thin, mature, fibrous septae. The tumors were unencapsulated and showed aggressive infiltration of the surrounding muscle and perineural tissues. Most of the clear cells contained cytoplasmic glycogen. Immunocytochemically, the tumor cells were positive for pan-keratin, cytokeratin 19, and epithelial membrane antigen, but were negative for vimentin, S100 protein, desmin, smooth muscle actin, human melanoma antigen (HMB-45), and α1-antichymotrypsin. Follow-up data showed 4 of 5 patients to have multiple local recurrences, and 1 of these 4 had submandibular lymph node metastasis and a fatal outcome due to uncontrollable tumor growth.

Conclusion.—These results suggest that odontogenic clear cell neoplasms are at least low-grade malignancies and should be classified as carcinomas.