Human Pathology

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2010-02-01

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2010-02-01

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2010-02-01

In This Issue

2010-02-01

Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features

2009-09-17

Summary: The 2004 World Health Organization classification system for urothelial neoplasia classifies flat-related preneoplastic lesions as urothelial hyperplasia (flat and papillary), reactive urothelial atypia, urothelial atypia of unknown significance, urothelial dysplasia (low-grade intraurothelial neoplasia), and urothelial carcinoma in situ (high-grade intraurothelial neoplasia). Each lesion is defined with precise nomenclature and strict morphologic criteria. In many cases, morphologic features alone suffice for diagnosis. Other cases may require a panel of immunohistochemical antibodies consisting of cytokeratin 20, p53, and CD44 for diagnosis. Recent molecular studies have provided further insight into the premalignant potential of these urothelial lesions. Herein, we present a review of flat urothelial lesions of the urinary bladder as defined by the 2004 World Health Organization classification with focus on the clinicopathologic, immunohistochemical, and molecular features.

Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases

Matthew J. Wasco, Stephanie Daignault, Deborah Bradley, Rajal B. Shah — 2009-10-05

Summary: Nested urothelial carcinoma (UC) is a rare histologic variant of UC, characterized by deceptively bland histologic features resembling von Brunn's nests but usually with a poor outcome. In our experience, this variant is frequently misclassified or underrecognized as its clinicopathologic spectrum is not well defined. In addition, its relationship to usual UC and response to traditional bladder cancer management are largely unknown. Herein we report the largest series to date of 30 UC cases with pure or predominant nested morphology to identify its associated histopathologic findings, clinical outcome, and immunophenotype. Patient age ranged from 41 to 83 years (average, 63 years) with a male-female ratio of 2.3:1. The architectural pattern of the nested component ranged from a predominantly disorderly proliferation of discrete, small, variably sized nests (90%) to focal areas demonstrating confluent nests (40%), cordlike growth (37%), and cystitis cystica-like areas (33%) to tubular growth pattern (13%). The deep tumor-stroma interface was invariably (100%) jagged and infiltrative. Despite overall banal cytology, tumor nests demonstrated focal random cytologic atypia (90%) and focal high-grade cytologic atypia centered within the base of the tumor (40%). The tumor stroma ranged from having minimal stromal response to focally desmoplastic and myxoid. A component of usual UC was present in 63% of cases. The nested component demonstrated an immunophenotype identical to usual UC, with CK7, CK20, p63, and CK903 expression in 93%, 68%, 92%, and 92% of cases, respectively. At resection, all but 1 case demonstrated invasive carcinoma—9% into lamina propria, 4% into muscularis propria, 65% into perivesical fat, and 17% into adjacent organ(s). When compared with pure high-grade UC, nested UC was associated with muscle invasion at transurethral resection (31% versus 70%; P < .0001), extravesical disease at cystectomy (33% versus 83%; P < 0.0001), and metastatic disease (19% versus 67%; P < .0001). Follow-up was available on 29 patients (97%) with a median of 12 months (range, 1-31 months) of follow-up; 3 (10%) died of disease, 16 (55%) are alive with persistent or recurrent disease, and 10 (34%) are alive without disease. Response to neoadjuvant chemotherapy was observed in 2 (13%) of 15 patients. Nested UC seen either in pure form or with a component of usual UC had similarly unfavorable outcomes (P = .78). Increased awareness and familiarity with the clinicopathologic spectrum is critical for confident recognition and adequate management of this very aggressive variant of UC.

Encapsulated thyroid tumors of follicular cell origin with high grade features (high mitotic rate/tumor necrosis): a clinicopathologic and molecular study

2009-11-16

Summary: Encapsulated thyroid tumors of follicular cell origin with high-grade features (EFHG) are unusual neoplasms. In current classification schemes, they are called atypical adenomas or follicular, papillary, or poorly differentiated carcinoma. When noninvasive, EFHG create a major therapeutic/diagnostic dilemma stemming from their rarity, low-stage, high-grade appearance, and lack of long-term follow-up studies. All cases of EFHG were defined as encapsulated tumors of follicular cell origin with at least 5 mitoses per 10 high-power fields and/or tumor necrosis. Available tissues were subjected to a thyroid carcinoma platform for mass spectrometry high-throughput genotyping, which consisted of 111 known mutations in 16 different genes: BRAF, RET, NRAS, HRAS, KRAS, PIK3CA, AKT1, and other related genes. Twenty-five cases met the selection criteria. Tumor necrosis was present in 56.0% (n = 14). Extensive vascular invasion was identified in 24.0% (n = 6). Eight (32%) of 25 tumors were noninvasive. Twenty-two patients (88%) were free of disease (median follow up: 8.5 years). All 8 noninvasive tumor did not recur despite focal/extensive tumor necrosis in 3 cases and a median follow-up of 11.9 years. EFHG with no vascular invasion did not recur. In patients without distant metastases at presentation (n = 24), 33% (2/6) of patients with extensive angioinvasion relapsed, whereas none of 18 with absent/focal vascular invasion recurred (P = .054). Mutations were found in 10 (45%) of 22 cases tested: 8 had NRAS codon 61, 1 KRAS codon 61, and 1 had coexistent BRAF V600E and AKT1. There was a higher frequency of RAS (9/22, 41%) than BRAF mutations (1/22, 4.5%) (P = .009). Noninvasive EFHG have an indolent behavior even in the presence of extensive tumor necrosis. EFHG with absent vascular invasion have an excellent prognosis despite the frequent occurrence of tumor necrosis. NRAS mutations are the most frequent oncogenic event in EFHG.

H3K4 dimethylation in hepatocellular carcinoma is rare compared with other hepatobiliary and gastrointestinal carcinomas and correlates with expression of the methylase Ash2 and the demethylase LSD1

2009-11-09

Summary: Methylation of core histones regulates chromatin structure and gene expression. Recent studies have demonstrated that these methylation patterns have prognostic value for some tumors. Therefore, we investigated dimethylation of histone H3 at lysine 4 (H3K4diMe) and H3K4 methylating (Ash2 complex) and demethylating enzymes (LSD1) in carcinomas of the hepatic and gastrointestinal tract. High levels of H3K4diMe were rarely observed in 15.7% of hepatocellular carcinoma (8/51) unlike other carcinomas including, in ascending order, cholangiocellular carcinoma/adenocarcinoma of the extrahepatic biliary tract, gastric carcinoma, pancreatic ductal adenocarcinoma, and neuroendocrine carcinoma (P < .001). Ash2 was expressed in 84.4% of hepatocellular carcinomas (38/45) and correlated directly with H3K4diMe modification (correlation coefficient r = 0.53) and LSD1 expression (r = 0.35). In contrast to other carcinomas, 65.9% (29/44) of hepatocellular carcinomas analyzed showed no LSD1 expression (P < .001). Interestingly, hepatocellular carcinomas without LSD1 expression appeared to be frequently Ash2 and H3K4diMe weak or negative (P = .004). In summary, high H3K4diMe expression is rare in hepatocellular carcinoma compared with other carcinomas (negative predictive value 92.3%), which may aid in the differential diagnosis. Lack of H3K4diMe is possibly due to complex epigenetic regulation involving Ash2 and LSD1.

Highly concordant coexpression of aromatase and estrogen receptor β in non–small cell lung cancer

2009-10-05

Summary: Estrogen receptor expression has been reported in non–small cell lung cancer. We examined the correlation between aromatase, a key enzyme in the synthesis of estrogen, and estrogen receptor expressions in 105 non–small cell lung cancer cases. All patients were older than 60 years, and all female patients were postmenopausal. Estrogen receptor α and progesterone receptor were detected in only 1 and 14 cases, respectively. Estrogen receptor β and aromatase were positive in 75 and 89 cases respectively. Estrogen receptor β expression in non–small cell lung cancer showed an inverse correlation with lymph node metastasis (P < .05). Only among females, both estrogen receptor β and aromatase expressions were correlated with higher Ki-67 labeling index and younger age (P < .05). Among 89 aromatase-positive cases, 70 were positive for estrogen receptor β, demonstrating a significant concordance (P < .05). Simultaneous immunohistochemical staining for aromatase and estrogen receptor β showed a high rate of double positive association. Male non–small cell lung cancer cases with double positivity for aromatase and estrogen receptor β demonstrated lower status in N factor by TNM classification (P < .05). In addition, among 89 aromatase-positive cases, a low-Allred total score of estrogen receptor β showed a significant relationship with large tumor size and high T factor by TNM classification (P < .05). In conclusion, frequent coexpression of aromatase and estrogen receptor β in non–small cell lung cancer might suggest some functional correlation between aromatase and estrogen receptor β, whereas estrogen receptor β negativity might be correlated with malignant progression of non–small cell lung cancer.

Does protein expression predict recurrence of benign World Health Organization grade I meningioma?

Vesa Kärjä, Pär-Johan Sandell, Tarja Kauppinen, Irina Alafuzoff — 2009-10-05

Summary: The aim of this study was to assess the predictive value of recurrence of protein expression in surgical samples of meningiomas. Thus, the expression of proteins that have been reported to be associated with prognosis of meningiomas was assessed in a sample of 59 World Health Organization grade I tumors obtained after Simpson grade I to III surgical resection (complete excision) and that were followed for 6 to 16 years. The expression was investigated applying immunohistochemical and tissue microarray techniques. One protein, the hepatocytic growth factor receptor, of 22 investigated proteins, showed significantly differing expression when comparing the 38 nonrecurrent with the 21 recurrent World Health Organization grade I meningiomas. It is noteworthy however that by means of logistic regression analyses, the independent predictive value of this protein expression was not significantly associated with the recurrence. Furthermore, it is noteworthy that the proliferation rate estimated by means of Ki67 expression did not show a significant difference, being 3.3 ± 0.4 for the nonrecurrent meningioma and 3.9 ± 0.5 for the recurrent and ranging from 0% to 10%. A significant and differing Spearman rank order of correlation was noted between 19 pairs of the investigated proteins when comparing nonrecurrent with recurrent World Health Organization grade I meningiomas. None of these correlations, however, showed a significant association by means of logistic regression analyses. Our results indicate that the Simpson grade significantly alters the outcome of a World Health Organization I grade meningioma and a longer follow-up period significantly increases the risk of recurrence. The expression of none of the proteins or correlation between protein expressions previously reported to be of significance regarding recurrence can be recommended as a diagnostic tool while assessing the risk of recurrence of World Health Organization grade I meningiomas.

Immunohistochemical analysis for Sox9 reveals the cartilaginous character of chondroblastoma and chondromyxoid fibroma of the bone

Eiichi Konishi, Yasuaki Nakashima, Yoko Iwasa, Ryuta Nakao, Akio Yanagisawa — 2009-10-05

Summary: Chondroblastoma, which is histologically composed of mononuclear cell proliferation and lobules of immature cartilage, and chondromyxoid fibroma, which is composed of myxoid lobules with spindle or stellate cells and a cellular fibrous rim with spindle cells, are both rare tumors. Based on histogenetic investigation including immunohistochemistry, matrix biochemistry, and electron microscopy, chondroblastoma is thought to contain chondrogenic cells, whereas chondromyxoid fibroma is considered to contain myofibroblastic cells, as well as chondrogenic cells, and chondroid matrix. In this study, we performed immunohistochemical analysis for Sox9, which is an essential transcriptional factor for chondrogenesis, to examine the possible chondrogenic nature of chondroblastoma and chondromyxoid fibroma. Formalin-fixed, paraffin-embedded tissues obtained from 10 cases of chondroblastoma and 11 cases of chondromyxoid fibroma were immunostained with antibody to Sox9. In addition, immunohistochemical study for collagen type II, which is a major component of cartilaginous matrix, was performed. Sox9 was positive in 8 chondroblastomas and 10 chondromyxoid fibromas. Positive staining was observed in the nuclei of the tumor cells. The matrices of 7 chondroblastomas and of 8 chondromyxoid fibromas were immunopositive for collagen type II. The findings suggest the cartilaginous differentiation of chondroblastoma and chondromyxoid fibroma.

N-myc downstream regulated gene-1/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin

2009-10-05

Summary: N-myc downstream regulated gene-1 (NDRG1)/Cap43 plays an important role in tumor progression and metastases in many kinds of cancers. Recently, it was reported that NDRG1/Cap43 is involved in the aggressiveness of prostate cancer and also that its expression is associated with the expression of E-cadherin in prostate carcinoma cell lines. In the current study, to elucidate the functional and pathologic roles of NDRG1/Cap43 in prostate cancer, we investigated whether the expression of NDRG1/Cap43 is associated with the clinicopathologic parameters of prostate cancer or E-cadherin expression. NDRG1/Cap43 expression and E-cadherin expression were examined immunohistochemically in 148 patients with prostate cancer. We investigated the correlation between membranous or cytoplasmic expression of NDRG1/Cap43 and E-cadherin and evaluated the prognostic or clinicopathologic significance of the expression of NDRG1/Cap43. The patients with decreased NDRG1/Cap43 membranous expression showed significantly lower disease-free survival rates compared with the patients with preserved NDRG1/Cap43 membranous expression. Decreased membranous and high cytoplasmic NDRG1/Cap43 expression was also correlated with a higher Gleason score. A significant correlation was observed between NDRG1/Cap43 membranous expression and E-cadherin membranous expression (r = 0.7130; P < .0001) and between NDRG1/Cap43 cytoplasmic expression and E-cadherin cytoplasmic expression (r = 0.5847; P < .0001). Decreased NDRG1/Cap43 membranous expression had a significant impact on patient disease-free survival in multivariate analysis (P = .0175). NDRG1/Cap43 could be a novel marker for malignant progression and poor prognosis in prostate cancer, plausibly in its close association with the down-regulation of E-cadherin expression.

Development of consensus guidelines for the histologic recognition of microscopic esophagitis in patients with gastroesophageal reflux disease: the Esohisto project

2009-10-05

Summary: No gold standard test exists for gastroesophageal reflux disease (GERD). Diagnostic difficulties are greatest when reflux symptoms occur without visible esophageal mucosal damage at conventional endoscopy. However, two thirds of such patients do have microscopic esophageal lesions. This study aimed to develop and standardize criteria for recognizing these microscopic esophageal lesions in GERD. Draft histologic criteria were developed and tested by an international group of 5 independent gastrointestinal pathologists using 167 biopsy specimens from GERD patients and healthy controls (phase I). Draft criteria were refined and reassessed using 250 photographs of biopsy specimens (phase II). Histologic lesions evaluated were basal cell hyperplasia, papillary elongation, intraepithelial eosinophil, neutrophil and mononuclear cell number, necrosis/erosion, healed erosion, and dilated intercellular spaces. Interobserver agreement and κ values increased significantly from phase I to II. When tested in annotated photographs (phase II), mean pairwise agreements were 74%, 89%, 93%, 97%, 81%, 97%, 94%, and 74%, respectively. Mean pairwise κ estimates (±SD) were 0.49 (0.16), 0.81 (0.05), 0.87 (0.05), 0.84 (0.09), 0.60 (0.09), 0.90 (0.04), 0.73 (0.14), and 0.61 (0.08), respectively. Estimated intraclass correlation coefficients for basal cell layer thickness and papillary length increased from 0.38 and 0.56 to 0.69 and 0.95, respectively, when revised criteria were used. The draft criteria achieved promising levels of agreement when assessed independently by 5 pathologists. Further steps include evaluation of lesions without indicating the area to be assessed and exploring the correlation of microscopic esophagitis with symptoms and esophageal acid exposure.

Isochromosome 12p and polysomy 12 in primary central nervous system germ cell tumors: frequency and association with clinicopathologic features

2009-10-05

Summary: Germ cell tumors arising within the central nervous system are rare neoplasms that typically occur along midline structures in children and young adults. Although isochromosome 12p is established as a frequent chromosomal abnormality in testicular germ cell tumors, studies examining isochromosome 12p in primary central nervous system germ cell tumors are limited. Herein, we studied 24 primary central nervous system germ cell tumors from 23 patients using fluorescence in situ hybridization to determine the frequency of isochromosome 12p in these neoplasms. Of the 24 primary central nervous system germ cell tumors, fluorescence in situ hybridization detected isochromosome 12p in 6 (25%) tumors, whereas 11 (46%) tumors showed polysomy (multiple copies) of chromosome 12. One case with isochromosome 12p also showed increased 12p independent of isochromosome 12p formation. The remaining 7 tumors yielded a normal result by fluorescence in situ hybridization. Clinical follow-up of this patient cohort indicated 8 patients (32%) developed a recurrence, although no association was demonstrated between the presence or absence of chromosomal 12 abnormalities and tumor relapse. We confirm that isochromosome 12p is less frequent in primary central nervous system germ cell tumors relative to testicular germ cell tumors, and although our numbers are limited, the presence or absence of isochromosome 12p does not appear to impact tumor recurrence. Similarly, although polysomy 12 was identified in nearly half of our central nervous system germ cell tumors, no prognostic significance was attributed to this abnormality. These results suggest that fluorescence in situ hybridization studies for isochromosome 12p or polysomy 12 may have limited use in the evaluation of these rare neoplasms.

Refractory remodeling of the microenvironment by abnormal type V collagen, apoptosis, and immune response in non-small cell lung cancer

2009-10-15

Summary: Collagen V shows promise as an inducer of the death response via caspases. Remodeling of the microenvironment by collagen V, tumoral/vascular apoptosis, and the immune response were evaluated, based on the prognosis of 65 patients with surgically excised non-small cell lung cancer. Immunofluorescence, immunohistochemistry, morphometry, tridimensional reconstruction, and a real-time polymerase chain reaction were used to evaluate the amount, structure, and molecular chains of collagen V, tumoral and vascular apoptosis, immune cells, and microvessel density. The impact of these markers was tested on follow-up until death from recurrent lung cancer occurred. A decreased and abnormal synthesis of collagen V was found to lead to increased angiogenesis due to a low endothelial death rate and a low immune response. A Cox model analysis, controlled for the lymph node stage, demonstrated that only collagen V and vascular apoptosis variables were significantly associated with survival time. A point at the median for collagen V and vascular apoptosis divided patients into 2 groups, each with a distinctive prognosis. Those with a collagen V higher than 9.40% and vascular apoptosis higher than 1.09% had a low risk of death (0.27 and 0.41, respectively) compared to those with a collagen V lower than 9.40% and vascular apoptosis lower than 1.09%. Collagen V and vascular apoptosis in resected non-small cell lung cancer was strongly related to the prognosis, suggesting that strategies aimed at preventing low collagen V synthesis, or local responses to low vascular apoptosis may have a greater impact in lung cancer treatment.

Imprint cytology detects floating Brachyspira in human intestinal spirochetosis

2009-10-16

Summary: Human intestinal spirochetosis is a colorectal infectious disease caused by 2 Brachyspira species. Its diagnosis is established by histology, culture, and polymerase chain reaction, but the value of cytologic examination in routine practice remains unclear. In this study, imprint cytology of biopsy specimens was examined for cytologic features specific to human intestinal spirochetosis. Specimens were obtained from 65 colorectal regions (1–3 regions from each case) in 25 ultrastructurally and/or genetically confirmed human intestinal spirochetosis cases (20 with Brachyspira aalborgi, 3 with B pilosicoli, 2 with both genotypes). In cytologic specimens, spirochetes tended to be floating freely within the mucus and intestinal fluid, whereas the “fringe formation” of spirochetes typically observed in histologic specimens was indistinct in cytologic specimens. Spirochetes were identified in 58 regions (89.2%) and 23 cases (92.0%) by cytology, against in 50 regions (76.9%) and 22 cases (88.0%) by histology (no significant differences). In 6 of 8 regions exhibiting positive cytology and negative histology, B pilosicoli was present within the mucus. Hence, B pilosicoli may tend to float in the mucus. In conclusion, cytologic examination would be useful for the routine identification of human intestinal spirochetosis, especially if B pilosicoli is involved. Further, we suggest the existence of differences in biological behavior between these spirochetes.

Progressive loss of selenium-binding protein 1 expression correlates with increasing epithelial proliferation and papillary complexity in ovarian serous borderline tumor and low-grade serous carcinoma

2009-11-09

Summary: Ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma often show a spectrum of histologic components with increasing epithelial proliferation and papillary complexity from flat cyst wall, hierarchical structures (with primary papillae branching into secondary papillae), micropapillae, and invasive carcinoma. Although tremendous research has been carried out to elucidate the causes of these tumors, the pathogenesis remains unclear. Literature has described a relationship between insufficient selenium intake and increased risk of cancer. The anticancer action of selenium has been suggested to be mediated by selenium-binding protein 1 as selenium-binding protein 1 is decreased in several cancers. The aim of the study was to examine by immunohistochemistry the expression of selenium-binding protein 1 in the various histologic components within ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma. Our study consisted of 62 cases of ovarian serous borderline tumor, 11 of micropapillary serous borderline tumor, and 7 of low-grade serous carcinoma. Review of archival slides showed flat cyst wall in 69 cases, primary and secondary papillae of hierarchical structures in 75 cases, micropapillae in 26 cases, microinvasion in 1 case, and frankly invasive carcinoma in 7 cases. The strongest immunoreactivity of selenium-binding protein 1 was seen in epithelial cells of flat cyst wall and primary papillae, followed by secondary papillae of the hierarchical structures. Micropapillae and invasive carcinoma (including microinvasion) exhibited a near complete loss of selenium-binding protein 1 expression. Selenium-binding protein 1 immunoreactivity remained the same regardless of the size of the micropapillae. Similar selenium-binding protein 1 expression was seen in the same histologic components from either ovarian serous borderline tumor or micropapillary serous borderline tumor. The gradual loss of selenium-binding protein 1 associated with increasing epithelial proliferation and papillary complexity indicates that selenium-binding protein 1 is involved in tumorigenesis of ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma. Our findings may provide a basis for future studies concerning the molecular mechanisms of selenium-binding protein 1 in tumorigenesis as well as a possible role of selenium in chemoprevention and treatment of ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma.

p53 expression in tumor-stromal fibroblasts is closely associated with the nodal metastasis and outcome of patients with invasive ductal carcinoma who received neoadjuvant therapy

2009-10-16

Summary: The purpose of this study was to determine whether p53 immunoreactivity in tumor-stromal fibroblasts assessed by the Allred scoring system in biopsy specimens obtained before neoadjuvant therapy and assessed in surgical specimens obtained after neoadjuvant therapy is significantly associated with nodal metastasis by invasive ductal carcinoma and with the outcome of 318 patients with invasive ductal carcinoma who received neoadjuvant therapy, according to UICC pathologic TNM stage, in multivariate analyses with well-known clinicopathologic factors. The Allred scores for p53 in tumor-stromal fibroblasts in the surgical specimens were significantly associated with the presence of nodal metastasis. The Allred scores for p53 in the tumor-stromal fibroblasts of biopsy and surgical specimens were a very important outcome predictive factor for patients who received neoadjuvant therapy, independent of UICC pathologic TNM status, but the outcome predictive power of the Allred scores for p53 in tumor-stromal fibroblasts assessed in the surgical specimens was superior to that of the Allred scores for p53 in tumor-stromal fibroblasts in the biopsy specimens. The results indicated a close association between p53 protein expression in tumor-stromal fibroblasts, especially in surgical specimens, and both the presence of nodal metastasis and the outcome of invasive ductal carcinoma patients who received neoadjuvant therapy.

CD81 protein is expressed at high levels in normal germinal center B cells and in subtypes of human lymphomas

2009-12-09

Summary: CD81 is a tetraspanin cell surface protein that regulates CD19 expression in B lymphocytes and enables hepatitis C virus infection of human cells. Immunohistologic analysis in normal hematopoietic tissue showed strong staining for CD81 in normal germinal center B cells, a cell type in which its increased expression has not been previously recognized. High-dimensional flow cytometry analysis of normal hematopoietic tissue confirmed that among B- and T-cell subsets, germinal center B cells showed the highest level of CD81 expression. In more than 800 neoplastic tissue samples, its expression was also found in most non-Hodgkin lymphomas. Staining for CD81 was rarely seen in multiple myeloma, Hodgkin lymphoma, or myeloid leukemia. In hierarchical cluster analysis of diffuse large B-cell lymphoma, staining for CD81 was most similar to other germinal center B cell–associated markers, particularly LMO2. By flow cytometry, CD81 was expressed in diffuse large B-cell lymphoma cells independent of the presence or absence of CD10, another germinal center B-cell marker. The detection of CD81 in routine biopsy samples and its differential expression in lymphoma subtypes, particularly diffuse large B-cell lymphoma, warrant further study to assess CD81 expression and its role in the risk stratification of patients with diffuse large B-cell lymphoma.

Any proportion of ductal adenocarcinoma in radical prostatectomy specimens predicts extraprostatic extension

Hemamali Samaratunga, David Duffy, John Yaxley, Brett Delahunt — 2009-12-11

Summary: Ductal adenocarcinoma of the prostate is an aggressive malignancy, often presenting at an advanced stage. In mixed ductal and acinar adenocarcinomas, the relationship between the proportion of the ductal component of the tumor and the pathologic stage and whether or not aggressive behavior is simply a function of grade remains undetermined. From 268 consecutive radical prostatectomies undertaken as a curative procedure for clinical localized prostate cancer, we identified 34 cases (12.7%) with ductal adenocarcinoma of the prostate comprising 5% to 100% of the total tumor volume. For cases with a ductal adenocarcinoma of the prostate component, the mean age at diagnosis of 60 years (range 49-69 years), mean serum prostate-specific antigen of 8.4 ng/mL (range, 0.8-21 ng/mL) and positive surgical margin rate of 17.6% did not differ significantly from that of the pure adenocarcinoma group. All 34 patients with ductal adenocarcinoma of the prostate had peripheral zone involvement while 16 (46%) also had transition zone involvement. Twenty-five (73%) cases with ductal adenocarcinoma of the prostate had extraprostatic extension (pT3), which compared to 32.9% with acinar adenocarcinoma. The presence of ductal adenocarcinoma of the prostate (P < .0001), high tumor volume (P = .001) and Gleason score >7 (P = .04) significantly predicted pT3 staging category, and the presence of ductal adenocarcinoma of the prostate remained a significant predictor for pT3, after adjusting for tumor volume and Gleason score >7. The proportion of ductal adenocarcinoma of the prostate did not significantly modify the strength of the observed association with pathological stage. In view of the significant association with extraprostatic extension we would recommend that in both core biopsies and radical prostatectomy specimens any proportion of ductal adenocarcinoma of the prostate should be reported.

t(8;21)(q22;q22) Translocation involving AML1 and ETO in B lymophoblastic leukemia

Huan-You Wang, Carlos A. Tirado — 2009-11-09

Summary: t(8;21)(q22;q22) giving rise to RUNX1/RUNX1T1 fusion transcript is a recurrent non-random chromosomal translocation, accounting for approximately 5% of cases of acute myeloid leukemia and 10% of acute myeloid leukemia with maturation. Studies have demonstrated so far that t(8;21)(q22;q22) occurs only in acute myeloid leukemia, and B lymphoblastic leukemia with t(8;21)(q22;q22) has not been reported in the literature. In the present study, we report a 44-year-old woman with a diagnosis of a B lymphoblastic leukemia based on morphology and immunophenotype. Conventional cytogenetic studies have shown a complex cytogenetic abnormality, notably and surprisingly, a t(8;21)(q22;q22) translocation. Interphase and metaphase fluorescent in situ hybridization have revealed a RUNX1/RUNX1T1 fusion signal on derivative chromosome 8 but not on chromosome 21, confirming the unbalanced translocation between chromosomes 8q22 and 21q22 involving both the RUNX1 and RUNX1T1 genes. The significance of this novel finding and its clinical applications has been further discussed.

Invasive ductal breast cancer within a malignant phyllodes tumor: case report and assessment of clonality

2009-11-09

Summary: Invasive carcinomas arising within fibroepithelial tumors represent an uncommon manifestation of breast cancer. We report the case of a 70-year-old woman who underwent mastectomy for a malignant phyllodes tumor measuring 6 cm. Histological workup of the specimen revealed a high-grade invasive ductal carcinoma 2.5 cm in diameter within the phyllodes tumor. DNA was isolated from microdissected epithelial and stromal components of the phyllodes tumor as well as from the invasive ductal carcinoma cells. Using multiplex polymerase chain reaction, a comparative allelotyping was performed with a panel of 11 microsatellite markers. The malignant stroma of the phyllodes tumor showed loss of heterozygosity at chromosome 16q23, 17q12, 17q25, and 22q13; the epithelial tumor component shared the loss of 16q23; whereas the invasive carcinoma had lost divergent alleles at 16q23, 17q12, and 17q25, indicating a lack of clonality between phyllodes tumor and invasive ductal carcinoma. Although our data are compatible with a previously postulated common origin of epithelial and stromal components of phyllodes tumors, the coexisting invasive ductal carcinoma appears to represent a true collision tumor.

Extranodal Rosai-Dorfman disease presenting as a cardiac mass in an adult: report of a unique case and lack of relationship to IgG4-related sclerosing lesions

2009-12-07

Summary: Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy) is a rare disease of unknown etiology that typically presents as nodal disease in young children. However, it also can present in various extranodal sites and can be difficult to recognize if not considered in the differential diagnosis. We describe a 55-year-old man who was discovered to have extranodal Rosai-Dorfman disease that presented as a cardiac mass involving the left atrium and ventricle during evaluation for atypical chest pain, and discuss the clinical, radiologic, and pathologic findings as well as treatment approach and consideration of a possible relationship of this entity to IgG4-related sclerosing lesions.

Virginia A. LiVolsi — 2009-12-11

This is the long-awaited update of the Armed Forces Institute of Pathology Fascicle on tumors of the breast. This edition is totally rewritten by new authors, Drs Tanya Tavassoli and Vincenzo Eusebi.

HER-2 amplification is highly homogenous in gastric cancer

2009-11-16

We have read the article of Marx et al with great interest because it focuses on HER2 expression in gastric cancer, a tumor that is very likely to become one of the next indications for HER2-targeted therapy using trastuzumab .

HER-2 amplification is highly homogenous in gastric cancer—reply

Andreas H. Marx, Ronald Simon, Guido Sauter — 2009-12-11

We very much appreciate the comments by Bilous et al further expanding the important discussion on HER2 amplification and overexpression in gastric cancer. The data provided by Bilous et al are to a large extent consistant with our findings. For example, their unpublished tissue multi array (TMA) study of 170 gastric cancer cases showed strikingly similar results: In 19.4% (n = 33) of the cases gene amplification strongly correlated with protein overexpression (as compared to 16% in our series of 166 gastric cancers). Bilous et al also strongly corroborate our observation of a strong association of protein overexpression and gene amplification; 23 of their 24 3+ cases (95.8%) and 4 of 9 2+ cases (44%) showed gene amplification. Our study revealed 100% amplification in 22 immunohistochemistry (IHC) 3+ and 83.3% (5/6) IHC 2+ cases .

Erratum to “Primary squamous cell carcinoma of the stomach with paraneoplastic leukocytosis: a case report and review of the literature” [Hum Pathol 40 (2009) 1494-1498]

2010-02-01

In the abovementioned article, the first author has noted that his surname was misprinted in the original article. The correct name should read “David Callacondo.”

Human Pathology

Masthead

Editorial Board

Information for Authors

Table of Contents

In This Issue

Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features

Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases

Encapsulated thyroid tumors of follicular cell origin with high grade features (high mitotic rate/tumor necrosis): a clinicopathologic and molecular study

H3K4 dimethylation in hepatocellular carcinoma is rare compared with other hepatobiliary and gastrointestinal carcinomas and correlates with expression of the methylase Ash2 and the demethylase LSD1

Highly concordant coexpression of aromatase and estrogen receptor β in non–small cell lung cancer

Does protein expression predict recurrence of benign World Health Organization grade I meningioma?

Immunohistochemical analysis for Sox9 reveals the cartilaginous character of chondroblastoma and chondromyxoid fibroma of the bone

N-myc downstream regulated gene-1/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin

Development of consensus guidelines for the histologic recognition of microscopic esophagitis in patients with gastroesophageal reflux disease: the Esohisto project

Isochromosome 12p and polysomy 12 in primary central nervous system germ cell tumors: frequency and association with clinicopathologic features

Refractory remodeling of the microenvironment by abnormal type V collagen, apoptosis, and immune response in non-small cell lung cancer

Imprint cytology detects floating Brachyspira in human intestinal spirochetosis

Progressive loss of selenium-binding protein 1 expression correlates with increasing epithelial proliferation and papillary complexity in ovarian serous borderline tumor and low-grade serous carcinoma

p53 expression in tumor-stromal fibroblasts is closely associated with the nodal metastasis and outcome of patients with invasive ductal carcinoma who received neoadjuvant therapy

CD81 protein is expressed at high levels in normal germinal center B cells and in subtypes of human lymphomas

Any proportion of ductal adenocarcinoma in radical prostatectomy specimens predicts extraprostatic extension

t(8;21)(q22;q22) Translocation involving AML1 and ETO in B lymophoblastic leukemia

Invasive ductal breast cancer within a malignant phyllodes tumor: case report and assessment of clonality

Extranodal Rosai-Dorfman disease presenting as a cardiac mass in an adult: report of a unique case and lack of relationship to IgG4-related sclerosing lesions

HER-2 amplification is highly homogenous in gastric cancer

HER-2 amplification is highly homogenous in gastric cancer—reply

Erratum to “Primary squamous cell carcinoma of the stomach with paraneoplastic leukocytosis: a case report and review of the literature” [Hum Pathol 40 (2009) 1494-1498]