Human Pathology

Masthead

2012-02-01

Editorial Board

2012-02-01

Information for Authors

2012-02-01

In This Issue

2012-02-01

Erythroid proliferations in myeloid neoplasms

Sa A. Wang, Robert P. Hasserjian — 2011-12-12

Summary: Prominent erythroid proliferations (in which erythroid elements comprise ≥50% of total bone marrow cells) can be seen in various hematopoietic stem cell neoplasms. The myeloproliferative neoplasm polycythemia vera exhibits effective, overexuberant erythropoiesis resulting in an increased red blood cell mass; in contrast, most other diseases characterized by erythroid predominance exhibit ineffective hemopoiesis. The latter include acute erythroid leukemia (erythroid-myeloid and pure erythroid leukemia subtypes) as well as some cases of myelodysplastic syndromes, acute myeloid leukemia with myelodysplasia-related changes, and therapy-related myeloid neoplasms. Some nonneoplastic reactive conditions may also manifest a striking bone marrow erythroid predominance. In this article, we review the literature relevant to this group of diseases for a better understanding of their clinicopathologic features and surrounding controversies. We also examine the position of neoplastic erythroid proliferations in the current 2008 World Health Organization Classification of Myeloid Neoplasms and provide recommendations as to how to approach the differential diagnosis of this group of diseases.

On being a pathologist—passing on the torch of knowledge

Lawrence M. Roth — 2012-02-01

Ours was a family that valued education. My father, Herman Moe Roth, was an engineer and physicist. Before marriage, my mother, Blanche Brown, was a high school English teacher in Canadian, Oklahoma, a small rural town in the southeastern part of the state. She had studied at Washington University in St. Louis for a year and then completed her education at the University of Oklahoma in Norman. My father obtained his undergraduate degree in electrical engineering from the University of Virginia in Charlottesville. He earned his PhD in astrophysics at the Mendenhall Laboratory of Physics of Ohio State University in Columbus during the great depression. He was the only surviving boy among 7 children and used to joke that he got the education and his sisters each got a dowry. Before World War II, he taught physics at what is now Oklahoma State University in Stillwater. During the war, he served in the US Army in the Corps of Engineers at Fort Belvoir, Virginia, and in Washington, DC. After World War II, he took a position with the Atomic Energy Commission in Oak Ridge, Tennessee, and later became director of research. He encouraged my brother, Sanford Irwin Roth, and me to pursue higher education. I followed my brother's footsteps and pursued medicine and ultimately the specialty of pathology. My maternal grandfather, Joseph Brown, was also pleased that we became physicians but would have preferred that we had become “real doctors,” meaning that we would take care of patients.

Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma

2011-08-05

Summary: The progression of intestinal metaplasia to esophageal adenocarcinoma in patients with Barrett's esophagus is partly driven by chromosomal alterations that activate oncogenes and inactivate tumor suppressor genes. The goal of this study was to determine how alterations of 4 frequently affected genes correlate with the range of histopathologic lesions observed in resected esophagi of patients with Barrett's esophagus. Fluorescence in situ hybridization was used to assess 83 tissue sections from 10 Barrett's esophagus esophagogastrectomy specimens for chromosomal alterations of 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2), and 20q13.2 (ZNF217). Histologic lesions assessed included gastric metaplasia (n = 8), intestinal metaplasia (n = 43), low-grade dysplasia (n = 28), high-grade dysplasia (n = 25), and adenocarcinoma (n = 16). Histologic maps showing the correlation between fluorescence in situ hybridization abnormalities and corresponding histology were created for all patients. Chromosomal abnormalities included 9p21 loss, single locus gain, and polysomy. A greater number of chromosomal alterations were detected as the severity of histologic diagnosis increased from intestinal metaplasia to adenocarcinoma. All patients had alterations involving the CDKN2A gene. CDKN2A loss was the only abnormality detected in 20 (47%) of 43 areas of intestinal metaplasia. Polysomy, the most common abnormality in dysplastic epithelium and adenocarcinoma, was observed in 16 (57%) of 28 low-grade dysplasia, 22 (88%) of 25 high-grade dysplasia, and 16 (100%) of 16 adenocarcinoma. The findings of this study improve our understanding of the role that chromosomal instability and alterations of tumor suppressor genes such as CDKN2A and oncogenes such as ERBB2 play in the progression of intestinal metaplasia to adenocarcinoma in patients with Barrett's esophagus.

The CIC-DUX4 fusion transcript is present in a subgroup of pediatric primitive round cell sarcomas

Cassandra Graham, Susan Chilton-MacNeill, Maria Zielenska, Gino R. Somers — 2011-08-03

Summary: Pediatric undifferentiated soft tissue sarcomas are a group of diagnostically challenging tumors. Recent studies have identified a subgroup of undifferentiated soft tissue sarcomas with primitive round to plump spindle cell morphology and a t(4;19)(q35;q13.1) translocation resulting in the expression of a CIC-DUX4 fusion transcript, including 2 tumors previously reported by our laboratory (Cancer Genet Cytogenet 2009;195:1). In the present study, reverse transcriptase polymerase chain reaction assays developed for both frozen and paraffin-based tissues were applied to a series of 19 pediatric undifferentiated soft tissue sarcomas using a combination of primer sets covering the CIC-DUX4 fusion transcript. Of the 19 undifferentiated soft tissue sarcomas, 16 had primitive round to plump spindle cell morphology, and 3 had pure spindle cell morphology. Three of the 16 undifferentiated soft tissue sarcomas with primitive round cell morphology were found to harbor the CIC-DUX4 fusion transcript by reverse transcriptase polymerase chain reaction. Automated DNA sequencing of the polymerase chain reaction products identified 2 distinct transcript variants. One CIC-DUX4–positive tumor showed membranous CD99 positivity, 2 showed focal S100 positivity, and 1 showed focal CD57 positivity. With the 2 previously reported cases, the total number of CIC-DUX4–positive primitive round cell sarcomas identified at our institution has been brought to 5 (28%) of 18. Given the consistent involvement of the CIC-DUX4 fusion in a subset of primitive round cell undifferentiated soft tissue sarcomas, these findings suggest a central role for the fusion transcript in such tumors. The current findings further define a novel genetic subset of pediatric primitive round cell sarcomas and provide an additional diagnostic tool for their characterization and diagnosis.

Warty/basaloid penile intraepithelial neoplasia is more prevalent than differentiated penile intraepithelial neoplasia in nonendemic regions for penile cancer when compared with endemic areas: a comparative study between pathologic series from Paris and Paraguay

2011-08-11

Summary: Penile squamous cell carcinoma shows an ample geographic variation in its prevalence with regions of low (North America, Europe, Japan, and Israel) and high (Africa, Asia, and South America) incidence. However, the geographic variation in the distribution of penile intraepithelial neoplasia is not well established. The aim of the present study was to compare the distribution of in situ and invasive lesions between geographic areas with low (France) and high (Paraguay) penile cancer incidence using a series of consecutive cases. The French series included 86 cases (57 in situ and 29 in situ + invasive squamous cell carcinoma), and the Paraguayan series, 117 cases (31 in situ and 86 in situ + invasive squamous cell carcinoma). Incidence of invasive squamous cell carcinoma in the overall samples was higher in the Paraguayan series (P < .00001). Comparing the Paraguayan and the French series, differentiated penile intraepithelial neoplasia was more prevalent in the former (65.0% versus 19.8%), whereas lesions showing warty and/or basaloid features predominated in the latter (35.0% versus 80.2%) to a significant level (P < .00001). This distinctive pattern of differential distribution was maintained when cases with associated invasive squamous cell carcinoma were excluded. The pattern of distribution of lichen sclerosus was also distinctive, with a significantly higher prevalence in the Paraguayan population when compared with the French series (32.5% versus 12.8%, P = .0015). In summary, there appears to be a distinctive distribution of penile precursor lesions depending on the geographic region in consideration. Penile intraepithelial neoplasia with warty and/or basaloid features predominated in low-incidence areas, whereas differentiated penile intraepithelial neoplasia was more prevalent in endemic regions for penile cancer. Further prospective studies in matched populations and from different geographic regions are needed to further clarify the reasons for this discrepancy.

Metallothionein expression in colorectal cancer: relevance of different isoforms for tumor progression and patient survival

2011-08-05

Summary: Metallothioneins are a family of small, cysteine-rich proteins with many functions. Immunohistochemical evaluation of all metallothionein 1 + 2 isoforms in colorectal tumors has demonstrated an important down-regulation compared with normal tissue, although its prognostic significance is unclear. Moreover, the contribution of individual isoforms to overall metallothionein down-regulation is not known. To address these important issues, we analyzed the messenger RNA expression levels of all functional metallothionein 1 + 2 isoforms by quantitative reverse transcription polymerase chain reaction in 22 pairs of normal and tumor-microdissected epithelia and correlated these to the overall immunohistochemical protein expression. Our results showed that 5 isoforms (MT1G, 1E, 1F, 1H, and 1M) were lost during the transition from normal mucosa to tumor, whereas MT1X and MT2A were less down-regulated, and their expression was correlated with overall protein positivity. Second, we showed that MT1G hypermethylation occurred in cell lines and in 29% of tumor samples, whereas histone deacetylase inhibitors are able to induce most isoforms. Furthermore, we analyzed by immunohistochemistry 107 normal mucosae, 25 adenomas, 81 carcinomas, and 19 lymph node metastases to evaluate metallothionein expression during different stages of cancer development and to assess its relationship to patient survival. A lower immunohistochemical expression was associated with poorer survival, although it was not an independent predictor. Overall, this study identifies for the first time the relevant metallothionein isoforms for colorectal cancer progression, supports the concept that their loss is associated with worse prognosis, and suggests 2 mechanisms for epigenetic repression of metallothionein expression in colorectal tumors.

Folliculocentric B-cell–rich follicular dendritic cells sarcoma: a hitherto unreported morphological variant mimicking lymphoproliferative disorders

2011-08-11

Summary: We report three cases of follicular dendritic cell sarcoma (FDCS) showing a hitherto undescribed histological pattern consisting of nodular tumor growth associated with small B lymphocytes. FDCS tumor cells consistently showed large epithelioid features and were intermingled with small lymphocytes in the nodules in two cases, whereas they formed cohesive aggregates surrounded by lymphocyte mantle in the other. These features were easily confused with lymphomatous proliferations and, in particular, subtypes of Hodgkin lymphoma, high-grade follicular lymphoma, and germinotropic large B-cell lymphomas. The diagnosis was established by the use of a broad panel of antibodies that showed a variable expression of the FDC markers CD21, CD23, CD35, clusterin, podoplanin, claudin 4, epidermal growth factor receptor, and CXCL13. The associated B lymphocytes revealed a mantle zone B phenotype, with expression of CD20 and PAX5, together with TCL1 and IgD. Of notice, in all cases, morphological features suggesting hyaline-vascular Castleman disease were recognized in the interfollicular areas, containing scattered epithelioid cells similar to those found in the nodules, thus providing a useful clue for FDCS diagnosis. Of the 3 cases, 1 presented multiple recurrences unresponsive to chemotherapy and radiotherapy and finally died of disease 14 years after diagnosis. This study further emphasizes the extreme variability of morphological presentation of FDCS and expands the spectrum of lesions showing a nodular growth pattern occurring in human lymph nodes.

Anal duct carcinoma: a report of 5 cases

Zina Meriden, Elizabeth A. Montgomery — 2011-08-05

Summary: Anal duct carcinoma (ADC) is a rare lesion composed of glands undermining non-neoplastic squamous epithelium. We describe the clinicopathologic characteristics and follow-up of 5 cases of ADC. Four definitive cases had tissue available for immunohistochemistry (IHC; CK7, CK20, prostate-specific antigen [PSA], estrogen/progesterone receptors [ER/PR], and p16) and in situ hybridization (ISH) for high-risk human papillomavirus (HR-HPV); a fifth case, with a history of ADC, had limited tissue for immunolabeling with only CK7, CK20, and p16. The mean patient age was 69.8 years. All 5 cases were CK7-positive and p16-negative. Four of 5 cases were CK20-negative. All cases with sufficient tissue (4/4) were negative for HR-HPV by ISH, PSA-negative (men), and ER/PR-negative (women). Four of 5 patients had previous malignancies, and in all 4 cases with sufficient tissue, metastasis was excluded with IHC. Of 5 patients, 3 developed metastases, whereas 2 had isolated local recurrences. ADCs are neoplasms with metastatic potential and can result in poor outcomes.

Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer

2011-08-05

Summary: Cancer cells show a higher rate of anaerobic respiration than normal cells. The exact mechanisms for this higher glycolysis rate in cancer cells remain to be elucidated. The results of recent studies have indicated that p53, the most commonly mutated tumor suppressor gene, may have important functions in the regulation of energy-generating metabolic pathways that switch from oxidative phosphorylation to glycolysis via the synthesis of cytochrome c oxidase 2 (SCO2), p53-transactivated TP53-induced glycolysis (TIGAR), and apoptosis regulator. We evaluated the expression of p53, SCO2, TIGAR, and COX in 113 cases of invasive breast cancer using immunohistochemistry. A high expression of p53, SCO2, TIGAR, and COX was noted in 27.5% (31 cases), 84.1% (95 cases), 74.3% (84 cases), and 73.4% (83 cases) of the breast tumors, respectively. A high p53 expression was significantly associated with low expression levels of SCO2 (P = .008), COX (P < .0001), and TIGAR (P = .007). On the survival analysis, the low SCO2-expressing breast cancer patients showed a significantly poorer prognosis than that of the high SCO2-expressing breast cancer patients (P = .0078). These results suggest that p53 can modulate the metabolic pathways via the proteins SCO2 and TIGAR in human breast cancer.

Immunoreactivity to caspase-3, caspase-7, caspase-8, and caspase-9 forms is frequently lost in human prostate tumors

2011-07-29

Summary: Caspases are essential initiators and executioners of apoptosis. Changes in their expression may contribute to the development of proliferative disorders such as cancer, by altering the death-proliferation homeostatic balance. The aim of this work was to analyze the expression of a broad panel of caspases at the epithelial level in human prostate tissues to assess possible prostatic disease–related alterations. We comparatively analyzed by immunohistochemistry the expression of pro–caspase-3, pro–caspase-8, pro–caspase-9, cleaved caspase-3, cleaved caspase-8, and caspase-7, in normal and pathologic (benign hyperplasic, premalignant [high-grade intraepithelial neoplasia], and cancerous [prostate cancer]) human prostate epithelium. Expression of caspases was correlated with clinicopathologic features, including preoperative prostate-specific antigen levels, Gleason scores, and biochemical progression. Percentage of positive samples for all the analyzed caspases decreased in prostate cancer versus normal prostate epithelium. The values obtained for benign prostatic hyperplasia and high-grade intraepithelial neoplasia more qualitatively resembled those of the prostate cancer group. Our results indicate that caspase expression in prostate malignant cells is reduced in a substantial number of patients and that such an alteration occurs in the premalignant stage. Loss of caspase expression could constitute a useful marker for prostate cancer diagnosis. Therapeutic approaches aimed to recover or enhance caspase expression might be effective against prostate cancer.

Dysplastic lesions in inflammatory bowel disease show increased positivity for the stem cell marker aldehyde dehydrogenase

Adam D. Toll, Bruce M. Boman, Juan P. Palazzo — 2011-08-05

Summary: The chronic inflammatory state in patients with inflammatory bowel disease places them at a substantially elevated risk for developing colorectal carcinoma. Moreover, distinguishing an inflammatory phenotype from dysplasia in inflammatory bowel disease can be difficult and has significant patient management implications. To this end, we studied the expression of the cancer stem cell marker aldehyde dehydrogenase to determine whether expression is increased in dysplastic lesions arising in inflammatory bowel disease. We studied 54 patients with inflammatory bowel disease who underwent surgical resection. Of the 54 patients, 13 exhibited high-grade dysplasia or adenocarcinoma, 19 exhibited low-grade dysplasia, and 22 displayed only inflammatory atypia. Staining for aldehyde dehydrogenase was evaluated in the cytoplasm of epithelial and stromal cells. We determined the intensity of staining (0 to 3+) and the percentage of cells staining positively. Positive staining for aldehyde dehydrogenase was observed in 92% (12/13) of cases with high-grade dysplasia/adenocarcinoma and in 95% (18/19) of cases with low-grade dysplasia. Cases with inflammatory atypia showed positive staining in 45% (10/22) of cases. The sensitivity for aldehyde dehydrogenase in epithelial cells as a marker for dysplasia was 95%; specificity was 55%. For stromal cells adjacent to dysplasia, sensitivity was 44%; and specificity was 68%. Although the sensitivity of aldehyde dehydrogenase for dysplasia was excellent, specificity was less than ideal. Our findings support the hypothesis that dysplasia in inflammatory bowel disease is associated with increased aldehyde dehydrogenase positivity, which supports the cancer stem cell hypothesis.

Vulvovaginal myofibroblastoma: expanding the morphological and immunohistochemical spectrum. A clinicopathologic study of 10 cases

2011-08-05

Summary: We analyzed the clinicopathologic features of 10 cases of vulvovaginal myofibroblastoma to widen its morphological and immunohistochemical spectrum. Most tumors (8/10 cases) were located in the vagina. The patients' age ranged from 44 to 77 years, and tumor size ranged from 0.4 to 3 cm. Histologically, 5 tumors had the characteristics of vulvovaginal myofibroblastoma. In addition, we identified 3 cases composed of spindle-shaped cells arranged in short fascicles with intervening thick collagen bands, closely reminiscent of mammary myofibroblastoma. Notably, 1 case resembled Sertoli cell tumor, sclerosing type, because of its predominant cord-like arrangement. In another case, there were highly cellular areas composed of uniform-packed, rounded cells that, at low magnification, looked like a malignant “small round blue cell tumor.” A variably thick band of native connective tissue separated tumors from the overlying squamous epithelium even if, in 3 cases, tumor cells extended up to the epithelium. In 7 cases, a variable number of vessels showed perivascular hyalinization. Only rare mitotic figures were identified. All tumors were diffusely positive for vimentin, desmin, and CD99. A variable staining intensity was observed for CD34, Bcl-2, B-cell lymphoma 2 (Bcl-2) CD10, estrogen receptor, and progesterone receptor in most cases, but none expressed α-smooth muscle actin. We emphasize that vulvovaginal myofibroblastoma encompasses a morphological spectrum wider than previously described. The overlapping morphological and immunohistochemical features of vulvovaginal and mammary myofibroblastomas led us to speculate that these are related entities with morphological variations on a common basic theme likely dependent on anatomical location.

Characteristics of positive surgical margins in robotic-assisted radical prostatectomy, open retropubic radical prostatectomy, and laparoscopic radical prostatectomy: a comparative histopathologic study from a single academic center

2011-08-05

Summary: Studies detailing differences in positive surgical margin among open retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robotic-assisted laparoscopic radical prostatectomy are lacking. A retrospective review of all prostatectomies with positive surgical margin performed at our center in 2007 disclosed 99 cases, 6 (5%) of which were reinterpreted cases as having negative margins. Ninety-three cases were, therefore, included, corresponding to 37 retropubic radical prostatectomies, 19 laparoscopic radical prostatectomies, and 37 robotic-assisted laparoscopic radical prostatectomies. The relationship of positive surgical margin characteristics to clinicopathologic parameters and biochemical recurrence was assessed. The most commonly found positive surgical margin site was the apex/distal third in all groups (62% retropubic prostatectomies, 79% laparoscopic prostatectomies, 60% robotic-assisted prostatectomies). Total linear length of positive surgical margin sites was significantly correlated with preoperative prostate-specific antigen, preoperative prostate-specific antigen density, pT stage, and tumor volume (P ≤ .001). We found no significant differences among the 3 groups with respect to total linear length, number of foci, laterality, or location of positive surgical margin. The rate of biochemical recurrence was also comparable in the 3 groups. On univariate analyses, biochemical recurrence was significantly associated with preoperative prostate-specific antigen values, preoperative prostate-specific antigen density, Gleason score, number of positive surgical margins, and total linear length of positive surgical margin (P ≤ .02). Only preoperative prostate-specific antigen density and number of positive surgical margin foci were statistically significant (P ≤ .03) independent predictors of biochemical recurrence. We found no significant difference in positive surgical margin characteristics or biochemical recurrence among the 3 radical prostatectomy modalities. Preoperative prostate-specific antigen density and number of positive surgical margin foci were the only independent predictors of biochemical recurrence.

Sensitivity and specificity of finding of multinucleate trophoblastic giant cells in decidua in placentas from high-risk pregnancies

Jerzy Stanek, Jacek Biesiada — 2011-08-05

Summary: This is a retrospective analysis of sensitivity and specificity of clustered placental basal plate multinucleate trophoblastic giant cells for various clinical conditions and placental lesions associated with fetal and placental hypoxia. Selected clinical and placental parameters of 375 consecutive cases of placentas with clusters of multinucleate trophoblastic giant cell (at least 3 cells with at least 3 nuclei) in the decidua (study group) were compared with all remaining 2674 placentas concurrently studied (control group) in 20-week-or-more high-risk pregnancies. Multinucleate trophoblastic giant cell was found in 12.3% of placentas. The study group had statistically significantly more cases of preeclampsia, abnormal Dopplers, induction of labor, and cesarean sections, with its placentas lighter and with more common other hypoxic lesions than in the control-group placentas. The multinucleate trophoblastic giant cell prevalence negatively correlated with gestational age (R = −0.56), peaking at the turn of the second and the third trimesters of pregnancy and declining afterward, and most strongly correlated with the excessive amount of extravillous trophoblasts in the chorionic disc (R = +0.33). The sensitivity of multinucleate trophoblastic giant cells was, on average, 3 times lower than the specificity, the latter averaging greater than 90%. In conclusion, finding of multinucleate trophoblastic giant cells is not exclusively limited to uteroplacental malperfusion of preeclampsia but is also seen in other types of high-risk pregnancy and in association with other placental hypoxic lesions and patterns. Multinucleate trophoblastic giant cells most likely reflect a premature fusion of extravillous trophoblasts because of several factors, likely including also hypoxia. Being highly specific, finding the multinucleate trophoblastic giant cells is unlikely to give a false-positive result and therefore has high value in retrospectively explaining the perinatal morbidity and mortality.

High CD10 expression predicts favorable outcome in surgically treated lymph node–positive bladder cancer patients

Roland Seiler, Michael von Gunten, George N. Thalmann, Achim Fleischmann — 2011-08-11

Summary: CD10 predicts survival in different cancers. The prognostic significance in bladder cancer still has to be documented. One hundred fifty lymph node–positive bladder cancer patients were treated by cystectomy and standardized pelvic lymphadenectomy in curative intent. CD10 expression was evaluated in tissue microarrays (TMAs) constructed from histopathological normal urothelium, primary tumor (tumor center and invasion front), and corresponding lymph node metastases and correlated with tumor characteristics (stage, extracapsular extension, number, and total diameter of metastases) and survival. CD10 expression was successively lost from normal urothelium to primary tumor to metastases (P < .05) and decreased from the tumor center to the invasion front (P < .002). High CD10 expression in tumor center or invasion front (P < .05) but not in the metastases predicted favorable outcome; the prognostic information in the tumor center was independent from tumor stage and lymph node parameters. High CD10 expression level was not associated with specific tumor characteristics. A well-defined sampling strategy for TMAs allows detection of specific biomarker expression patterns and may generate prognostic information inherent in particular tumor areas. The favorable outcome in bladder cancer patients with high CD10 expression might suggest a tumor suppressive function of CD10.

High nuclear protein kinase Cθ expression may correlate with disease recurrence and poor survival in oral squamous cell carcinoma

2011-08-16

Summary: Protein kinase Cs play important roles in many biological processes and tumorigenesis. This study examined the expression of protein kinase Cθ and assessed its significance in patients with oral squamous cell carcinoma. Immunohistochemical staining was carried out to investigate the expression of protein kinase Cθ in 59 cases of oral squamous cell carcinoma. The results were correlated with clinical characteristics and outcome of patients. Diffuse cytoplasmic protein kinase Cθ was identified in 53 (89.8%) of the 59 oral squamous cell carcinoma cases, and the expression was not statistically associated with any clinicopathologic parameter. Twenty (40.7%) of the 59 oral squamous cell carcinoma cases exhibited nuclear expression of protein kinase Cθ with different grade of intensity. χ2 analysis indicated that high nuclear protein kinase Cθ expression correlated significantly with shorter 24-month survival (P = .043) and disease recurrence (P = .019). The Kaplan-Meier method also showed that high nuclear expression of protein kinase Cθ was significantly associated with poor overall survival (P = .034) and shorter time to recurrence (P = .003). Univariate analysis revealed that high nuclear protein kinase Cθ expression (P = .046; hazard ratio, 2.2), tumor size less than 2 cm (P = .049; hazard ratio, 4.7), lymph node metastasis (P = .003; hazard ratio, 3.0), and higher stage (P = .002; hazard ratio, 8.7) were each associated with shorter overall survival. We identified the aberrant nuclear expression of protein kinase Cθ in oral squamous cell carcinoma. High nuclear protein kinase Cθ expression may correlate with disease recurrence and poor survival in patients with oral squamous cell carcinoma.

Prognostic role of metastasis tumor antigen 1 in patients with ovarian cancer: a clinical study

2011-08-11

Summary: In this study, we investigated the prognostic value of metastasis tumor antigen 1 expression in 81 untreated patients with ovarian cancer. The expression of metastasis tumor antigen 1 was evaluated by immunohistochemistry, and staining was analyzed in relation to clinicopathologic variables, disease-free survival, and overall survival. High expression of metastasis tumor antigen 1 was found to be associated with advanced stage (I/II versus III/IV, P = .02) and with worse response to first-line treatment (P = .03). Cases with high metastasis tumor antigen 1 expression showed a lower disease-free survival compared with cases with low expression (P = .02). In multivariate analysis of disease-free survival, metastasis tumor antigen 1 overexpression retained an independent negative prognostic role (P = .04), when considered together with histotype, stage of disease, residual tumor at surgery, and chemosensitivity. The evaluation of the prognostic relevance of metastasis tumor antigen 1 in late-stage disease showed that overexpression was a prognostic factor for poor disease-free survival and overall survival in this subset of patients, in both univariate and multivariate models. These findings indicate that metastasis tumor antigen 1 overexpression can be used as a predictor of clinical outcome in patients with ovarian cancer and therefore may represent a new prognostic marker.

Tumor of the heart in a young woman; a rare manifestation of Wegener granulomatosis

Remmi Singh, Seymour Rosen — 2011-08-01

Summary: Wegener granulomatosis may rarely present with tumor masses that are in areas not typically involved by the disease. Although some cases have an associated positive anti-neutrophilic cytoplasmic antibodies, other cases do not, especially those of the limited form. To prevent misdiagnosis and ensure prompt treatment, it is extremely important to consider Wegener granulomatosis even in cases without the classic clinical findings. We report a case of a 19-year-old woman with no prior significant medical history who presented with persistent ventricular tachycardia and a papillary muscle mass in her left ventricle which upon excision and tissue evaluation demonstrated histologic changes of Wegener granulomatosis.

Cytogenetic and comparative genomic hybridization studies of an esophageal giant fibrovascular polyp: a case report

2011-08-11

Summary: Esophageal giant fibrovascular polyps are rare and are thought to represent redundant tumorlike or hamartomatous esophageal folds. Although most patients present with slowly evolving dysphagia, a minority present with acute respiratory distress or even death caused by asphyxia. We present the pathologic and cytogenetic findings of an 18-cm esophageal giant fibrovascular polyp in a 49-year-old woman who presented with odynophagia and dysphagia. The histologic findings are that of classic esophageal giant fibrovascular polyp as previously described in the literature. Cytogenetic study revealed an abnormal karyotype, and comparative genomic hybridization analysis showed regional amplifications of chromosomes 3 and 12 and a possible loss of 22q13.3-qter. The significance of these cytogenetic findings is unclear but may suggest a neoplastic process in the pathogenesis of esophageal giant fibrovascular polyps.

Ectomesenchymoma with t(1;12)(p32;p13) evolving from embryonal rhabdomyosarcoma shows no rearrangement of ETV6

2011-08-01

Summary: Ectomesenchymoma is a rare mesenchymal malignancy occurring mainly in the pediatric population. The hallmark diagnostic features are a combination of sarcoma, usually rhabdomyosarcoma (RMS) with admixed ganglion cells. The lesion arises either in soft tissues or the cranial cavity, and outcomes vary considerably. Current knowledge about the genetics and biology of ectomesenchymoma is extremely limited with only 4 published karyotypes, showing overlaps only in trisomies 2, 8, and 11. Here, we describe a case with genetic findings that, in conjunction with preexisting observations, offer some additional insights into the genetic aberrations of ectomesenchymoma.

Signet ring cell tumor of the minor salivary gland exhibiting benign behavior

2011-08-03

Summary: Signet ring cell (SRC) carcinomas are usually aggressive malignancies, arising most frequently in the stomach and gastrointestinal tract, but also, although less often, in other organs such as the breast, bladder, and lungs. They are particularly unusual in the salivary glands, and the aim of the present study is to report a case of a tumor of the minor salivary glands of the lower lip composed largely of SRCs but which displayed benign clinical behavior.

Indeterminate cell tumor of the spleen

2011-08-05

Summary: Indeterminate cell tumor is an extremely rare neoplasm that mainly occurs in the skin. We report a case of indeterminate cell tumor arising from the spleen, a previously unreported site for indeterminate cell tumor. Histologically, the tumor showed nests, nodules, and sheets of large polygonal cells with mostly oval nuclei; open chromatin; variable nucleoli; and abundant, eosinophilic cytoplasm. Some cells possessed irregularly convoluted nuclei with nuclear grooves and granular cytoplasm, suggestive of Langerhans cells. Immunohistochemically, the tumor cells were diffusely positive for S-100 and CD1a and negative for Langerin. No Birbeck granules were found by electron microscopy. Clinical and radiologic examination showed no other organomegaly or lymphadenopathy. A diagnosis of primary indeterminate cell tumor of the spleen was rendered. To the best of our knowledge, this is the first indeterminate cell tumor reported in the spleen. Biologic insights into dendritic cells in the spleen and the pertinent literature on these entities are reviewed.

Human Pathology

Masthead

Editorial Board

Information for Authors

Table of Contents

In This Issue

Erythroid proliferations in myeloid neoplasms

On being a pathologist—passing on the torch of knowledge

Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma

The CIC-DUX4 fusion transcript is present in a subgroup of pediatric primitive round cell sarcomas

Warty/basaloid penile intraepithelial neoplasia is more prevalent than differentiated penile intraepithelial neoplasia in nonendemic regions for penile cancer when compared with endemic areas: a comparative study between pathologic series from Paris and Paraguay

Metallothionein expression in colorectal cancer: relevance of different isoforms for tumor progression and patient survival

Folliculocentric B-cell–rich follicular dendritic cells sarcoma: a hitherto unreported morphological variant mimicking lymphoproliferative disorders

Anal duct carcinoma: a report of 5 cases

Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer

Immunoreactivity to caspase-3, caspase-7, caspase-8, and caspase-9 forms is frequently lost in human prostate tumors

Dysplastic lesions in inflammatory bowel disease show increased positivity for the stem cell marker aldehyde dehydrogenase

Vulvovaginal myofibroblastoma: expanding the morphological and immunohistochemical spectrum. A clinicopathologic study of 10 cases

Characteristics of positive surgical margins in robotic-assisted radical prostatectomy, open retropubic radical prostatectomy, and laparoscopic radical prostatectomy: a comparative histopathologic study from a single academic center

Sensitivity and specificity of finding of multinucleate trophoblastic giant cells in decidua in placentas from high-risk pregnancies

High CD10 expression predicts favorable outcome in surgically treated lymph node–positive bladder cancer patients

High nuclear protein kinase Cθ expression may correlate with disease recurrence and poor survival in oral squamous cell carcinoma

Prognostic role of metastasis tumor antigen 1 in patients with ovarian cancer: a clinical study

Tumor of the heart in a young woman; a rare manifestation of Wegener granulomatosis

Cytogenetic and comparative genomic hybridization studies of an esophageal giant fibrovascular polyp: a case report

Ectomesenchymoma with t(1;12)(p32;p13) evolving from embryonal rhabdomyosarcoma shows no rearrangement of ETV6

Signet ring cell tumor of the minor salivary gland exhibiting benign behavior

Indeterminate cell tumor of the spleen