Solid Adenocarcinoma Research Articles

Influence of Cigarette Smoking on Histological Subtypes of Stage I Lung Adenocarcinoma

The purpose of this study was to examine the association between cigarette smoking and histological subtypes of lung adenocarcinoma. We reviewed a total of 320 consecutive patients with stage I adenocarcinoma who underwent complete resections with systematic node dissections from January 2004 to December 2006 at the National Cancer Center Hospital East. A statistically significant difference was observed in recurrence-free probabilities between never smokers and ever smokers (3-year recurrence-free probabilities of 95.6% and 88.6%, respectively, p = 0.034). Among adenocarcinoma histological subtypes, only a solid component was significantly more frequent in ever smokers than in never smokers (p < 0.001). Among patients with solid components, significantly more cases had lymphatic permeation (p = 0.007), intratumoral vascular invasion (p < 0.001), and visceral pleural invasion (p < 0.001). Multivariate analysis revealed that ever-smoking history was the only statistically significant independent clinical predictor for a solid component (p < 0.001). Among ever smokers, smoking extent in pack-years of patients with solid components was significantly greater than that of those without solid components (p < 0.001). With respect to predominant subtypes, smoking extent in pack-years of patients with predominantly solid adenocarcinomas was significantly greater than that of patients with predominantly bronchioloalveolar carcinoma, papillary, or acinar adenocarcinomas (all p < 0.001). A greater smoking extent was associated with the presence of adenocarcinoma solid components, which may have more aggressive biological features resulting in poorer outcomes.

Prognostic Significance of a Solid Component in Pulmonary Adenocarcinoma

We retrospectively analyzed pulmonary adenocarcinoma patient survival in our single-institution database to evaluate the impact of solid adenocarcinoma components (SAC) on survival and to propose a method of incorporating SAC into the T classification in future staging systems. We reviewed 504 consecutive patients with surgically resected pulmonary adenocarcinoma for their clinicopathologic characteristics and prognoses, stratifying patients according to predominant adenocarcinoma subtype. We also stratified patients with an SAC-containing tumor according to the ratio of SAC in analyzing outcome. Patients with SAC (SAC+) had significantly poorer prognoses than patients without any SAC (SAC-), irrespective of SAC ratio. Patient groups stratified by pathologic T classification up to T2b could be divided into four categories according to SAC status in decreasing order of survival: (I) T1a/SAC-; (II) T1b/SAC-; (III) T1a/SAC+, T1b/SAC+, and T2a/SAC-; and (IV) T2a/SAC+ and T2b/SAC-. Pulmonary adenocarcinoma patients with any amount of SAC had worse prognoses than those without any SAC. The presence of SAC was an independent unfavorable prognostic factor, comparable to other pathologic findings indicating invasion. Solid adenocarcinoma component was an upstaging factor in T classification for T1 and T2a pulmonary adenocarcinomas. If SAC is present, we propose T1 and T2a tumors should be classified as T2a and T2b, respectively.

Endoscopic Ultrasound-Guided Fine Needle Aspiration of Pancreatic Cysts With and Without Antibiotic Prophylaxis: A Retrospective Analysis of Infectious Complications

Purpose: To determine the rate of infectious complications when endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is performed with and without prophylactic antibiotics. Methods: We evaluated 144 patients who underwent EUS-FNA of pancreatic cystic lesions between March 2003 and July 2009, with and without prophylactic antibiotics. A total of 190 endoscopic ultrasounds were evaluated. The procedures were performed in one center by two experienced endosonographers. The hospital's endoscopic database was used to identify all EUS-FNAs of pancreatic cystic lesions. Endoscopy procedure notes were reviewed to gather data, including patient demographics, cyst size and location, presence of septations, diagnosis, number of passes, needle size, inpatient or outpatient status, performance of same-day endoscopic retrograde cholangiopancreatography, and use of prophylactic antibiotics. An infectious complication was defined by fever, elevated white blood cell count >11 K/μL, positive blood cultures, or use of antibiotics for up to 30 days after the procedure. Data on complications were collected by performing a complete medical records review. These data were supplemented by telephone calls to the patients using a standard questionnaire. Results of available cytology and pathology were also noted. Patients were excluded if they underwent a cyst-gastrostomy or if a solid mass or pancreatic adenocarcinoma was diagnosed by FNA. Results: Of 190 procedures with FNA of a pancreatic cyst, 120 procedures did not receive prophylactic antibiotics and 70 did. In the procedures that did not receive antibiotics, four infectious complications were identified (3.33%): three had increased white blood cell count, and one had a positive blood culture. Of the procedures that did receive antibiotics, one was found to have an infectious complication (1.42%), a positive blood culture. Conclusion: Overall, the infectious complication rates among patients undergoing EUS-FNA do not appear to be greatly reduced by receiving prophylactic antibiotics as the rates are similar to those not receiving prophylactic antibiotics. Current recommendations call for antibiotic prophylaxis before EUS-FNA of cystic lesions along the gastrointestinal tract, with a fluoroquinolone as the preferred agent. However, this is a Grade 1C recommendation. Given the side effects associated with fluoroquinolones, larger randomized studies should be performed to justify the current recommendations.

Zone of transition: a potential source of error in tumor volume estimation.

To measure the width of the zone of transition (ZOT) between nonaerated solid tumor and surrounding nonneoplastic lung parenchyma and determine the extent to which ZOT influences computer-derived estimates of tumor volume based on computed tomographic (CT) images. This HIPAA-compliant study was approved by the institutional research board. The histologic slide containing the maximum tumor area was digitized for 20 consecutive patients with solid adenocarcinoma. The outer border of the tumor (A2) was marked; it included all lung parenchyma having any tumor cells. The inner border of the tumor (A1) was marked; it included only solid tumor where lung parenchyma was no longer preserved. Assuming two circles with areas of A2 and A1, the corresponding two radii, R2 and R1, were calculated. The average width of the ZOT was defined as R2 minus R1. The relationship between ZOT and tumor diameter on the CT images prior to surgery was assessed by using regression analysis. The relationship between ZOT and tumor volume was assessed by using a theoretical model of idealized spheres with varying diameters. The mean width of the ZOT was 0.78 mm (median, 0.48 mm). The proportional effect of ZOT on tumor volume estimates decreased with increasing tumor diameter and increased with increasing width of ZOT. Correlation between ZOT and tumor diameter was not significant (P = .87). The average width of ZOT is about a single pixel width on a full field of view CT scan; thus, the ZOT can have a large effect on volume estimates, particularly for small tumors.

A Case of Solid Adenocarcinoma Arising from the Cystic Duct with Tumor Thrombus in the Common Bile Duct

A Case of Solid Adenocarcinoma Arising from the Cystic Duct with Tumor Thrombus in the Common Bile Duct

From the authors:: Fig. 1—

In our paper 1, we summarised the expertise and practical guidelines we have built in recent years for the differential diagnosis and management of focal ground-glass opacities (GGOs) detected by spiral computed tomography (CT), either in a screening programme or incidentally. As J-J. Hung and co-workers rightly point out, malignant GGOs may show a mixed evolution pattern over time with a decrease in their overall size but an actual increase of the central solid component. This should not be mistaken for a regression, but rather for progression to solid adenocarcinoma 2. Regression in response to antibiotic trial was defined by us as fading or disappearance of the entire lesion, which occurred in five (12.5%) cases. Six patients were evaluated retrospectively, as their GGOs were visible on previous CT scans months before the lesion was actually reported. Antibiotics were not prescribed at that point as we did not expect them to have an effect on such lesions. …

Subepithelial myofibroblast in lung adenocarcinoma: a histological indicator of excellent prognosis

We report here the presence of subepithelial myofibroblasts in pure bronchioloalveolar carcinoma and a subset of invasive lung adenocarcinoma. The subepithelial myofibroblasts we describe were observed in a peculiar location beneath the cancer cells in the alveolar septa. Immunohistochemically, they were positive for α-smooth muscle actin and calponin, but negative for desmin and h-caldesmon. To gain insight into their biological significance, we examined 116 surgically resected lung adenocarcinomas. The resected tumors included 13 bronchioloalveolar carcinomas, 20 mixed type adenocarcinomas with bronchioloalveolar carcinoma components, 57 papillary adenocarcinomas, 22 solid adenocarcinomas with mucin, and 4 acinar adenocarcinomas. All specimens were immunostained for α-smooth muscle actin to visualize the myofibroblasts. In all of the pure bronchioloalveolar carcinomas observed, the subepithelial myofibroblasts were completely preserved adjacent to the cancer cells. In mixed adenocarcinomas with bronchioloalveolar carcinoma components, subepithelial myofibroblasts were present in the bronchioloalveolar carcinoma components, but scanty in the invasive areas, where stromal myofibroblasts emerged between the cancer cell nests. Subepithelial myofibroblasts were retained, however, in the invasive areas of a subset of invasive adenocarcinomas. Survival analysis showed that the retention of subepithelial myofibroblasts in these invasive tumors was associated with low rates of lymphatic and vascular invasion, a low rate of lymph node involvement, and an excellent patient survival. These results suggest that subepithelial myofibroblasts increase in bronchioloalveolar carcinomas, but are gradually replaced by typical stromal myofibroblasts during progression into invasive cancer. A subset of invasive adenocarcinomas retains subepithelial myofibroblasts. Analysis of subepithelial myofibroblasts may be helpful in identifying a subset of lung adenocarcinoma with excellent prognosis.

Wnt1 Expression Induces Short-Range and Long-Range Cell Recruitments That Modify Mammary Tumor Development and Are Not Induced by a Cell-Autonomous β-Catenin Effector

Xenograft model studies have shown that tumor-associated, or genetically modified, activated stromal cells can promote tumor cell growth. Here, we examined mammary tumors arising in response to two different transgene-mediated Wnt signaling effectors: Wnt1 (a ligand with cell-nonautonomous effects) and DeltaNbeta-catenin (a constitutively active form of the intracellular effector). Although the route of tumor development has been shown to be similar for these two models, histologic analysis shows that Wnt1-induced tumors are associated with tracts of activated stroma, whereas most DeltaNbeta-catenin-induced tumors are solid adenocarcinomas. Furthermore, quantification of the "reactive stroma index" indicates that abundant activated stroma correlates with accelerated tumor progression. Wnt1-expressing mammary epithelial cells induce Wnt-specific target gene expression in local stromal cells (Wnt1-induced secreted protein 1/CCN4) but also induce long-range effects. Thus, mice with rapid tumor progression have 2-fold more circulating endothelial progenitor cells in peripheral blood than control or DeltaNbeta-catenin transgenic mice. Using tagged bone marrow (BM) transplants, we show that BM-derived cells are massively recruited to infiltrate the stroma of Wnt1-induced tumors where they differentiate into multiple cell types. Thus, localized ectopic expression of the proto-oncogene Wnt1 in mammary glands induces systemic responses, and we propose that this response modifies the tumorigenic outcome.

Lung Adenocarcinoma: Modification of the 2004 WHO Mixed Subtype to Include the Major Histologic Subtype Suggests Correlations Between Papillary and Micropapillary Adenocarcinoma Subtypes, EGFR Mutations and Gene Expression Analysis

The histologic heterogeneity of lung adenocarcinoma creates a variety of complex challenges to pathologists in analyzing the various subtypes. Current classification schemas do not take into account the major subtype. We analyzed 100 cases for clinical, pathologic, and molecular features using a modification of the 2004 World Health Organization (WHO) classification to record the major component in the mixed subtype tumors. The tumors were analyzed for KRAS mutation and epidermal growth factor receptor (EGFR) by mutation, chromogenic in situ hybridization, and immunohistochemistry for EGFR and phosphorylated EGFR. Gene expression analysis was performed using HG-U133A Affymetrix oligonucleotide microarrays revealing 3 gene clusters. The most common major histologic subtype was papillary (37%) followed by acinar (30%), solid (25%) and bronchioloalveolar (7%) carcinoma (BAC), although no pure BACs were seen. Sixteen tumors harbored EGFR mutations and 14 KRAS mutations. Papillary adenocarcinoma strongly correlated with EGFR mutation (P<0.001) and gene profile Cluster 1 (P=0.006) with weaker correlations with low grade (P=0.038) and favorable behavior in Stage 1 patients (P=0.047). Micropapillary subtype correlated strongly with EGFR mutation (P<0.001) and weakly with Cluster 1 (P=0.030). Solid adenocarcinoma strongly correlated with gene profile Cluster 3 (P=0.001) and worse survival (P=0.001). BAC as a major component strongly correlated with gene Cluster 2 (P=0.001). Cluster 1 correlated strongly with less smoking (P<0.001), papillary histology (P<0.001), and EGFR mutations (P<0.001). Cluster 3 strongly correlated with heavier smoking (P<0.001), larger tumor size (P<0.001), solid subtype (P<0.001), and poor grade (P=0.004); weak correlations were found with KRAS mutation (P=0.025). No correlation was found with BAC and EGFR by mutation, chromogenic in situ hybridization or immunohistochemistry. Higher stage (P<0.001), grade (P<0.001), and solid subtype (P=0.001) correlated with shorter survival. Our data suggest that EGFR mutations are associated with papillary adenocarcinoma and gene profile Cluster 1. We discovered this only because we used a comprehensive approach examining in detail all histologic subtypes and we modified the 2004 WHO mixed subtype to include the major histologic subtype. As we do not know the major genetic pathways of 30% to 70% of lung adenocarcinomas, the comprehensive histologic subtyping we propose gives advantage for recognition of unanticipated histologic-genetic correlations that might not be detected using classification systems that focus primarily on specific aspects of adenocarcinomas such as BAC or EGFR mutations. Such an approach should be considered in future studies for validation in other datasets.

Spontaneous necrosis of solid gallbladder adenocarcinoma accompanied with pancreaticobiliary maljunction

A 71-year-old Japanese man with acute cholecystitis and an incarcerated gallbladder (GB) stone was admitted. Plain ultrasonography (US) incidentally detected a mass-like lesion in the fundus. Doppler US revealed that this elevated lesion had no blood flow. Computed tomography showed a relatively low-density mass, measuring 5 cm multiply 4 cm in diameter, with no positive enhancement. Magnetic resonance imaging showed a mass in the fundus with a slightly low intensity on T1-weighted images and a slightly high intensity on T2-weighted images. We were agonized in making the qualitative diagnosis of mass-like lesions of the fundus, such as a benign tumor, cancer, or debris. We performed laparoscopic cholecystectomy, because the incarcerated GB stone clearly caused acute cholecystitis. Intra-operative cholangiography clearly revealed pancreaticobiliary maljunction. Amylase levels in the common bile duct and gallbladder were quite high. The elevated lesion in the fundus clearly showed severe necrosis. Although this necrotic nodule included non-viable adenocarcinoma cells, viable cancer cell nests were located in the muscularis propria and subcutaneous layer. Histopathological examination confirmed a solid adenocarcinoma. Thus, we diagnosed it as a gallbladder cancer, based on histopathological analysis of the resected specimen. We therefore undertook radical surgery, including wedge resection of the liver, radical dissection of regional lymph nodes, and resection of the extrahepatic bile duct. Histopathological findings revealed no cancer, hyperplasia or dysplasia in the additionally resected specimens. The patient was finally staged as T2, N0, H0, P0, M(-), stage II. We present the first case of spontaneous necrosis of solid gallbladder adenocarcinoma, with a review of previous studies.

The correlation between stroma analysis and MDCT early phase contrast enhancement in small solid lung adenocarcinoma

Objective To evaluate correlations between proportion and distribution of tumor stroma and MDCT early phase enhancement character in solid lung adenocarcinoma, and compare with microvessel density and histological subtypes.

Co-expression of vimentin and cytokeratin in bitch mammary gland tumors

This work presents the results of immunohistochemical studies on the distribution of intermediary filamentous proteins vimentin and cytokeratin in bitch mammary gland tumors, which had been previously classified according to the latest WHO-classification (1999). The overall test specimen included 45 bitches of different breeds and age, which resulted in diagnosing 27 malignant neoplasms, 11 benign neoplasms, and 3 hyperplastic-dysplastic changes, while 4 test specimens were taken from healthy bitches. The commonest malignant neoplasms were: simple adenocarcinoma (13 cases) and complex adenocarcinoma (7). Among the benign neoplasms the ones that dominated were benign mixed tumors (8 cases). Vimentin was expressed on neoplastic proliferative suprabasal myoepithelial cells of simple adenocarcinomas; on resting, spindleshaped and star-shaped myoepithelial cells of complex adenocarcinomas; on cartilage cells of carcinomas in the mixed tumor and benign mixed tumors; on osteoid cells of osteosarcoma; and on myofibroblasts of simple adenocarcinomas, complex adenocarcinomas, carcinomas in the mixed tumor and benign mixed tumors, and connective tissue fibres of fibrosarcoma. The expression of cytokeratin was noticed on canalicular and alveolar lumen epithelium of simple adenocarcinomas; on epithelial cells of complex adenocarcinomas, carcinomas in the mixed tumor, mutinous carcinomas, fibrosarcoma and of osteosarcoma; on resting and starshaped myoepithelial cells of complex adenocarcinomas and carcinomas in the mixed tumor; as well as on spindle-shaped myoepithelial cells of carcinomas in the mixed tumor. Proliferative suprabasal myoepithelial cells of simple adenocarcinomas showed the co-expression of vimentin and cytokeratin, and so did the resting and spindle-shaped myoepithelial cells of complex tubular adenocarcinomas, whereas in complex solid adenocarcinomas the coexpression was also shown on star-shaped myoepithelial cells. The coexpression of vimentin and cytokeratin was found on resting myoepithelial cells of benign mixed tumors, simple and complex adenomas, and mammary gland hyperplasia; on spindle-shaped myoepithelial cells of benign mixed tumors, complex adenomas and myoepithelial solid adenomas; and on star-shaped myoepithelial cells of benign mixed tumors.

DC-LAMP stains pulmonary adenocarcinoma with bronchiolar Clara cell differentiation

DC-LAMP is a molecule expressed in mature dendritic cells, but its mRNA is also found in the lung. This study compares the immunostaining spectrum of PE-10, an antisurfactant protein monoclonal antibody; thyroid transcription factor-1 (TTF-1); and DC-LAMP in normal and neoplastic lung in an attempt to characterize the cell type(s) that express DC-LAMP. Electron microscopy was used to define cell types. DC-LAMP marks pulmonary adenocarcinomas that show Clara cell characteristics by electron microscopy. In contrast, PE-10 labels tumors that have Clara cell and type II pneumocyte differentiation. DC-LAMP staining was lost in solid type adenocarcinomas but persisted in well-differentiated areas. CC-10, an antibody that marks Clara cells, was also positive in tumors that labeled for DC-LAMP. There was no prognostic difference in tumors that reacted with DC-LAMP. DC-LAMP and CC-10 reactivity was also observed in endometrial adenocarcinomas but not in other tumor types.

Ectopic expression of N-acetylglucosamine 6-O-sulfotransferase 2 in chemotherapy-resistant ovarian adenocarcinomas

Mucinous and clear cell adenocarcinomas are the major histological types of ovarian epithelial cancer and are associated with a poor prognosis due to their resistance to chemotherapy. A novel tumor marker specific for ovarian mucinous and clear cell adenocarcinomas would be helpful for overcoming these serious diseases. We showed previously by enzymological characterization and RT-PCR that colonic mucinous adenocarcinoma tissues ectopically express GlcNAc6ST-2, a member of the carbohydrate 6-O-sulfotransferase family (Seko, A. et al. (2002) Glycobiology 12, 379-388). Here, we prepared a GlcNAc6ST-2-specific polyclonal antibody for immunohistochemical analysis and found that GlcNAc6ST-2 is ectopically expressed by not only colonic mucinous adenocarcinomas but also ovarian mucinous, clear cell and papillary serous adenocarcinomas. In contrast, solid serous adenocarcinomas, endometrioid adenocarcinomas, and mucinous adenomas expressed GlcNAc6ST-2 much less frequently or not at all. RT-PCR analysis confirmed that GlcNAc6ST-2 transcripts are expressed in ovarian mucinous adenocarcinomas but not in mucinous adenomas. In addition, immunohistochemical analysis using sulfated glycan-specific monoclonal antibodies showed that ovarian adenocarcinoma cells express GlcNAc 6-O-sulfated glycans, including an L-selectin ligand and its related glycans. These results indicate that GlcNAc6ST-2 would be a novel tumor antigen that is specifically expressed in ovarian mucinous, clear cell and papillary serous adenocarcinomas.

Prognostic Value of Histology in Resected Lung Cancer With Emphasis on the Relevance of the Adenocarcinoma Subtyping

Adenocarcinoma (AC) is the most common lung cancer, followed by squamous cell carcinoma (SCC). Controversy exists concerning both cell types. Our purpose was to compare their prognosis after resection and determine whether AC subtyping may have any significance. From 1993 to 2002, 574 patients with SCC and 565 with AC underwent a curative resection and were compared according to sex, age, type of resection, TNM system classification, and survival. One hundred fifty-nine patients with ACs demonstrated a pure histologic pattern according to the 1999 World Health Organization classification, and 406 were of the mixed subtype including cell types with potentially different aggressiveness. Therefore, we compared subgroups according to presence or not of bronchioloalveolar carcinoma or solid adenocarcinoma with mucin component, or both. Compared with ACs, SCCs had a higher number of males and older patients, and incidences of endobronchial tumors, pneumonectomies, and stage II tumors were higher. Global survival rates were not different. The ACs with solid AC with mucin components (n = 239) were characterized by more males and stage IIB patients, and had poorer survival rates (38.6% vs 61.4%; p < 0.0014) than the ACs without solid AC with mucin component. When comparing these with SCCs, 5-year survival rates were: ACs without solid AC with mucin component (58.1%), SCCs (50.2%), and ACs with solid AC with mucin component (36.8%) (p < 0.000019). Multivariate analysis demonstrated these subgroups and SCCs to be independent factors of prognosis. Solid ACs with a mucin component demonstrated the poorest prognosis after resection. Further studies of this cell type, which should be looked for carefully, may help improve targetting adjuvant therapies.

Appendiceal Mass in a Middle-Aged Woman

Appendiceal Mass in a Middle-Aged Woman

Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin

The latest World Health Organization (WHO) classification divides adenocarcinoma mainly into adenocarcinoma mixed subtypes, acinar adenocarcinoma, papillary adenocarcinoma, bronchioloalveolar carcinoma, and solid adenocarcinoma with mucin production, and it mentions several variants, including fetal adenocarcinoma, mucinous ("colloid") adenocarcinoma, mucinous cystadenocarcinoma, signet-ring adenocarcinoma, and clear cell adenocarcinoma. In general, the mucin-producing adenocarcinoma of the lung comprises signet-ring cell carcinoma (SRCC), solid adenocarcinoma with mucin production (SA), and mucinous bronchioloalveolar carcinoma (m-BAC), mucinous ("colloid") adenocarcinomas and/or mucinous cystadenocarcinoma, and mucoepidermoid carcinoma. As SRCC, SA, and m-BAC exhibit distinct clinical features, it is important to identify differences in their immunohistochemical characteristics to better understand their histogenesis. In this study we analysed SRCC, SA, m-BAC, normal lung, and foregut-related secretory tissue for immunohistochemical differences using tissue microarrays. SRCC and SA showed high expression of MUC1 (97.4% and 100%, respectively), cytokeratin (CK) 7 (both 100%), and thyroid transcription factor-1 (TTF-1) (81.1% and 100%, respectively). They also showed low expression of MUC5AC (25.5% and 21.1%, respectively) and MUC6 (18.3% and 10.5%, respectively), whereas m-BAC showed high expression of MUC5AC (97.5%), MUC6 (75.0%), and CK7 (94.7%), but low expression of MUC1 (57.5%), and TTF-1 (27.5%). Hierarchical clustering showed that the immunophenotypes of SRCC and SA belong to the same category as alveolar lining cells, whereas m-BAC clustered onto another branch with gastric foveolar cells and bronchial goblet cells. These immunohistochemical findings support the results of our previous clinicopathological analysis of SRCC of the lung showing that SRCC occurs anatomically in the peripheral portion of the lung rather than in the bronchial gland-bearing portion.

Association of Low-Grade Endometrioid Carcinoma of the Uterus and Ovary With Undifferentiated Carcinoma: A New Type of Dedifferentiated Carcinoma?

Low-grade endometrioid carcinomas, either of the endometrium or the ovaries, usually have an excellent prognosis. The association of this type of tumor with undifferentiated carcinoma is rare. In this study, we present the clinicopathologic features of 25 such cases. The age of the patients ranged from 30 to 82 years (median, 51 years). At presentation, the patients had either vaginal bleeding or pelvic pain. The endometrioid carcinoma involved the endometrium in 14 cases, the endometrium and 1 or both ovaries in 9 cases, and the ovaries in 2 cases. Undifferentiated carcinoma associated with low-grade endometrioid carcinoma was found at presentation in 19 grade 1 or 2 endometrioid carcinomas: 15 in the endometrium and 5 in the ovary. In one of these cases, undifferentiated carcinoma was found in the endometrium and the ovary. Undifferentiated carcinoma was found after resection of low-grade endometrioid carcinoma in six cases, involving the retroperitoneum, pelvis, vagina, or liver. The undifferentiated carcinoma was composed exclusively of diffuse sheets and solid nests of epithelial cells in l0 cases. Epithelial cells with isolated foci of keratinization were seen in nine cases and rhabdoid cells in a myxoid background in six cases. Twenty-four patients were treated with total abdominal hysterectomy and with bilateral salpingo-oophorectomy. Twenty-two patients received additional therapy as follows: chemotherapy (), radiotherapy (), and tamoxifen (). Follow-up showed that 15 patients died of disease in 1 to 60 months (median, 6 months), and 5 patients are alive with progressive disease with a follow-up between 6 and 8 months; 1 patient is alive with no evidence of disease at 104 months. In four cases, the diagnosis was made recently, with short follow-ups of 3 and 4 months. Foci of undifferentiated carcinoma may be confused with solid endometrioid adenocarcinoma erroneously leading to the diagnosis of a grade 3 or a significantly less aggressive grade 2 endometrioid carcinoma. The recognition of undifferentiated carcinoma in an otherwise low-grade endometrioid adenocarcinoma is extremely important because it indicates aggressive behavior. In asynchronous cases, being aware of this association can explain the absence of a second primary.

Endothelial cell apoptosis in the context of quantification of angiogenesis in solid human adenocarcinomas: A novel double immunolabelling technique to identify endothelial cell apoptosis

Standardised methods of microvessel density quantification have been published. However, a reliable and reproducible method to visualise endothelial cell apoptosis is lacking, which is a shortcoming in assessing vascular remodelling during angiogenesis. The aim of this study was to validate a newly developed technique to demonstrate endothelial cell apoptosis by double immunolabelling with anti-CD34 and anti-activated caspase-3 in human adenocarcinomas. Double immunolabelling was used to identify apoptotic endothelial cells in six tumours of eight different human adenocarcinomas. Microvessel density and rate of apoptotic endothelial cells were quantified. The technique revealed endothelial cell apoptosis simultaneously with the identification of microvessel density on one slide. These characteristics were reproducible in adenocarcinomas of various sites. In conclusion, apoptotic endothelial cells and microvessel density can now be evaluated simultaneously within one and the same area, allowing a more reliable histological quantification of angiogenesis.

Surfactant Protein A Detection in Primary Pulmonary Adenocarcinoma without Bronchioloalveolar Pattern

Background: Immunohistochemical studies in human lung carcinoma reported positive staining of tumor cells for surfactant protein A (SP-A), especially in peripheral airway cell carcinoma, which include bronchioloalveolar carcinoma and in some reports also papillary subtypes. Objective: The purpose of this study was to determine the SP-A expression in tumor cells of lung adenocarcinoma without a bronchioloalveolar pattern, classified according to the WHO. Methods: In total, 169 primary adenocarcinomas of the lung (109 acinar, 32 solid with mucin, 24 papillary and 4 mucinous) were examined by immunohistochemistry for SP-A expression. Results: Twenty-five percent of acinar, 38% of papillary and 3% of solid adenocarcinoma with mucin showed a positive intracytoplasmic SP-A reaction of the tumor cells. None of the mucinous adenocarcinomas stained for SP-A. This study included the largest number of acinar adenocarcinomas and solid adenocarcinomas with mucin studied for SP-A. We clearly demonstrated that also primary lung adenocarcinoma without a bronchioloalveolar pattern can express SP-A. A positive staining of hyperplastic type II cells surrounding the tumors or entrapped in the tumor could clearly be differentiated from the SP-A-positive stain of tumor cells. Conclusion: These results support the theory that SP-A-producing cells may generate not only bronchioloalveolar and papillary carcinoma, but also other subtypes of lung adenocarcinoma.