Ovarian metastases of intestinal-type gastric carcinoma: A clinicopathologic study of 4 cases with contrasting features to those of the Krukenberg tumor

Ovarian metastases of intestinal-type gastric adenocarcinomas are rare, and information on them is very limited compared with that on signet-ring cell carcinomas that result in the Krukenberg tumor. Four cases are reported herein. The patients averaged 55 years of age. In 3 patients, the ovarian metastases were identified several to 21 months after the diagnosis of the gastric primary, and the tumors were synchronous in the fourth. Two tumors were bilateral, 1 unilateral, and for 1, the laterality was unknown. The ovarian tumors were characteristically solid and cystic, with multinodular growth in 2. In 2 cases, the ovarian tumors had a pseudoendometrioid morphology with tubulo-glandular, cribriform, and papillary patterns; they also had focal trabecular and insular patterns. Prominent necrosis was present, including segmental and intraluminal "dirty" necrosis. In the other 2 cases, the ovarian tumors had a mucinous appearance, 1 being dominantly cystic with occasional goblet cells and the other with prominent foveolar-type cells. Nuclei ranged from deceptively bland to highly atypical. Surface implants were identified in 2 cases. Two ovarian tumors examined expressed cytokeratin 7 and 20 but not estrogen receptor. Three patients with follow-up information all died within 1 year of the ovarian metastases. Although information is limited, our results suggest that metastatic spread to the ovary by intestinal-type gastric adenocarcinoma is usually seen in patients older than those with Krukenberg tumors, with a known history of gastric carcinoma, and with concomitant widespread disease. Involvement of the ovary by intestinal-type gastric carcinoma produces a microscopic picture distinctly different from that of a Krukenberg tumor. These metastatic intestinal-type tumors may be confused with metastases from other gastrointestinal sites that are more frequently the cause of pseudoendometrioid or mucinous metastases, and like such tumors may be confused with primary ovarian endometrioid and mucinous neoplasms.     

Sinonasal Adenocarcinoma: Update on Classification,Immunophenotype and Molecular Features

Adenocarcinomas of the sinonasal tract may originate from respiratory surface epithelium or the underlying seromucinous glands. These malignancies are divided into salivary-type adenocarcinomas and non-salivary-type adenocarcinomas. The latter are further divided into intestinal-type and nonintestinal-type adenocarcinomas. This review provides an update on tumor classification, differential diagnostic considerations and molecular features, as well as new adenocarcinoma entities in the sinonasal area.     

A histochemical and ultrastructural study of adenocarcinoma of the lung.

Twenty-five cases of solitary nodular adenocarcinoma of the human lung were studied histochemically and ultrastructurally and their morphological characteristics were compared to the cells observed in the control lungs. Adenocarcinoma cells of the human lung may be classified into following four types: Type A--cells resembling the bronchial goblet cell; Type B--cells resembling the mucous cell of the bronchial gland; Type C--cells resembling the type II alveolar lining cell; and Type D--cells resembling the nonciliated bronchiolar cell. Twenty-one cases belonging to Type D (84%) and two cases to Type B (8%), and one case each to Types A (4%) and C (4%). For the histogenesis of adenocarcinoma of the human lung, nonciliated bronchiolar epithelium may be the most important. A comparison of 10 cases of bronchiolo-alveolar carcinoma with 15 cases of ordinary (acinar and papillary) adenocarcinoma revealed no clear differences either histochemically or ultrastructurally.     

Histological grading of alveolar type renal cell carcinoma based on architectural variation

Ninety-two of a total 107 renal cell carcinomas excluding papillary, sarcomatoid and other uncommon histological types were classified into 3 groups based on architectural variations. Statistically analyses were carried out for prognostic significance. Histological criteria of 3 groups were defined as follows. Group I consists predominantly of tubular formations with characteristic cystic change. Group III shows solid proliferation without tubular formations, and Group II shows small alveolar or trabecular structures with inconspicuous tubular formations. According to the survival curves (Kaplan-Meier method), the prognosis of Group I was significantly better than II and III. Ten year survival rate of each group was 88 +/- 7.8% in Group I, 39 +/- 8.8% in Group II, and 0% in Group III. The distribution of T and V stages in the 3 groups were not significantly different. Nuclear grading of Group I and II was not so different, though high grade cases predominated in Group III. Therefore, the present grading of alveolar type renal cell carcinoma based on architectural atypia was considered to be a useful prognostic parameter.     

Renal cell carcinomas in children and young adults: increased incidence of papillary architecture and unique subtypes.

Renal cell carcinomas in children and young adults are rare, and the pathologic features of these tumors have not been well described. We reviewed 24 renal cell carcinomas in children and young adults ages 6 to 29 years, 14 of whom were younger than 18 years of age. Fourteen were female. In 19 (79%) of 24 cases, the tumor met histologic criteria for papillary renal cell carcinoma, with at least 50% papillary architecture. Four of the remaining five cases were typical clear cell tumors in patients known to have von Hippel Lindau syndrome, and one case was of chromophobe type. In the papillary tumors, calcifications, high nuclear grade, extracapsular extension (American Joint Commission on Cancer stage T3), and lymph node metastases were common. Among these papillary tumors, four distinct histologic patterns could be identified. Collecting duct-like tumors (two cases) involved the large collecting ducts, were multifocal and predominantly papillary, and had focal tubular and solid areas. These tumors were reactive for epithelial membrane antigen (EMA) and keratins, including CK7, but negative for Ulex europeaus and high molecular weight keratin 34BE12. Voluminous cell tumors (four cases) were composed of cells with extremely voluminous clear cytoplasm and, although predominantly papillary, had areas that also resembled clear cell tumors. These tumors were reactive for keratins AE1/AE3 but were otherwise negative for all other keratins, EMA, and U. europeaus. One of these tumors showed an X;7 translocation. Adult type tumors (12 cases) resembled papillary tumors of adults. These tumors were reactive for EMA and keratins, including CK7, and all but one were negative for U. europeaus and keratin 34BE12. This last case had trisomies of chromosomes 7, 16, 17, and 20. The final neuroendocrinelike case was multifocal, organoid, and composed of nests of small cells in a neuroendocrinelike pattern. Three of 13 patients were alive with disease at last follow-up, and three additional patients died of disease, all within 2 years. Progression was highly associated with lymph node involvement at the time of resection. We conclude that the clinicopathologic features of renal cell carcinomas in children and young adults differ from those arising in older adults. These tumors are characteristically high-grade, high-stage, papillary tumors with numerous calcifications, and several subtypes can be identified based on histologic, immunohistochemical, and cytogenetic features. Some subtypes appear to be unique to this age group.     

Microcystic endocervical adenocarcinomas: a report of eight cases

Eight endocervical adenocarcinomas with a prominent cystic component that resulted in a resemblance, in part, to certain benign lesions are described. The patients ranged in age from 34 to 78 years (average age, 48.6 years), and three women were postmenopausal. Presentations included abnormal cervical cytology smears (n = 4) and vaginal bleeding (n = 3). One patient was pregnant at the time of diagnosis. Six tumors were typical endocervical-type and two tumors were intestinal-type adenocarcinomas. The cysts occupied 50% to approximately 90% of the tumor and ranged from 1 to 8 mm in diameter. They were lined by flattened to low cuboidal to pseudostratified epithelium with focal goblet cells and Paneth cells in the two intestinal-type tumors, and the epithelial lining of the cysts was denuded occasionally. Seven tumors contained luminal mucin, which was brightly eosinophilic in one patient and resembled the contents of mesonephric tubules, but was mucin positive on special stains. A desmoplastic stroma was identified in two patients; the remainder had no stromal reaction. The features that resulted in mimicry of benign lesions were the cystic glands, their sometimes orderly distribution, and focal, deceptively bland cytology. All tumors contained, at least focally however, architecturally abnormal glands lined by cytologically malignant cells.     

Carcinoma of the gallbladder--a clinical appraisal and review of 40 cases

Prognosis of 40 patients with gallbladder carcinoma who had undergone curative resection was investigated. Five-year survival rate calculated from Kaplan & Meier's method was 67% in 16 cases in Stage I, 43% in 8 cases in Stage II and 22% in 10 cases in Stage III, respectively. In 6 cases, classified as Stage IV, no case survived more than 2 years postoperatively. Most patients in Stage I had the tumors of papillary type in macroscopic appearance, papillary adenocarcinoma, and negative vascular and perineural invasions and showed better prognosis. In Stages II, III and IV, in contrast, most tumors were infiltrative or nodular type, tubular adenocarcinoma, and positive vascular and perineural invasions and demonstrated poorer prognosis. Patients in Stage I who had undergone simple cholecystectomy showed 5-year survival rate of 57%, and who underwent cholecystectomy with wedged resection of the gallbladder bed of the liver and regional lymphadenectomy (extended cholecystectomy) showed that of 100%. Extended cholecystectomy, therefore, is the procedure of choice in patients in Stage I. In patients in Stages II, III and IV, extended cholecystectomy yielded 5-year survival rate of 33%. More radical procedure or combined modality therapy must be indicated in advanced stage of the disease.     

Sinonasal adenocarcinoma: immunohistochemical marking and expression of oncoproteins

BACKGROUND: Relatively little is known concerning the immunohistochemical marking of sinonasal adenocarcinoma (SNA). The most clinically problematic tumors are those that seem histologically identical to colonic adenocarcinoma, a neoplasm that may metastasize to the sinonasal region. To determine whether differentiated immunohistochemical expression of keratins could differentiate primary from metastatic tumors and to understand the biology of these tumors, differentiated keratin and oncoprotein expression was investigated. METHODS: Eleven patients with sinonasal adenocarcinoma were investigated for expression of cytokeratins 7 and 20 (CK7, CK20), AE 1/3, CAM 5.2, smooth muscle-specific actin, muscle-specific actin, desmin, S-100, carcinoembryonic antigen (CEA), p53, and HER-2/neu. RESULTS: All sinonasal adenocarcinomas of intestinal type were cytokeratin 7 positive. None of the tumors showed myoepithelial differentiation. Strong HER-2/neu staining was seen in some tumors. CONCLUSIONS: Strong HER-2/neu staining in some cases suggests this oncogene may be involved in the genesis of SNA. Immunohistochemical staining with cytokeratin 7 may be potentially useful in differentiating primary from metastatic disease in sinonasal adenocarcinomas of the intestinal subtype.     

Primary and Secondary/ Metastatic Salivary Duct Carcinoma Presenting within the Sinonasal Tract

Traditionally, sinonasal adenocarcinomas have been subdivided into intestinal (ITAC) and non-intestinal (non-ITAC) categories. The latter encompasses salivary-type adenocarcinomas originating from the seromucinous glands of the sinonasal mucosa and non-salivary adenocarcinomas. The non-salivary adenocarcinoma category is further subdivided into low-and high-grade variants. Among salivary-type sinonasal adenocarcinomas, tumors recapitulating salivary duct carcinoma (SDC) are exceedingly rare, but some might have been lumped into the high-grade non-ITAC category. To date, only three primary SDCs originating in the sinonasal tract have been reported. We herein describe 7 cases of SDC including one previously reported case (4 primary sinonasal, 3 metastatic/ extension from parotid gland SDC). The primary tumors affected 3 males and one female aged 60 – 75. Different sites were involved by the primary tumors while the secondary tumors affected the sphenoidal (2) and the frontal + maxillary (1) sinuses. Three primary tumors were de novo high-grade SDC and one was confined to contours of a pre-existing pleomorphic adenoma. All 3 secondary tumors were SDC ex pleomorphic adenoma of the parotid with a long history of recurrences, ultimately involving the sinonasal tract. Androgen receptor was positive in 7/7 cases. Four of 6 cases were strongly HER2/neu + (either score 3 + or with verified amplification). This small case series adds to the delineation of primary sinonasal SDC highlighting that almost half of invasive SDC presenting within sinonasal tract indeed represents extension or metastasis from a parotid gland primary. There is a tendency towards overrepresentation of HER2/neu-positive cases in both categories (primary and metastatic), but this needs clarification in larger studies.     

Prognostic Value of Laurén Classification and c-erbB-2 Oncogene Overexpression in Adenocarcinoma of the Esophagus and Gastroesophageal Junction

Background: The prognostic value of the Laurén classification and of c-erbB-2 oncogene overexpression has been described for gastric cancer. The aim of this study was to investigate the clinical significance of these factors in adenocarcinoma of the esophagus and/or gastroesophageal junction (GEJ).Methods: Forty-one adenocarcinomas of the esophagus and/or GEJ were reviewed for tumor stage, lymph node status, Laurén classification, and c-erbB-2 overexpression, as assessed by immunohistochemical analysis.Results: According to the Laurén classification, tumors were classified as intestinal-, mixed-, or diffuse-type (54%, 32%, and 15%, respectively). Diffuse-type tumors were associated with a significantly worse prognosis than were intestinal-type tumors (P = .018; log-rank test). The prognostic value of the Laurén classification was independent of stage (P = .048; Cox regression model). Overexpression of c-erbB-2 was detected in 24% of the tumors and was present exclusively in intestinal-type tumors and in intestinal-type areas of mixed-type tumors. Ten of the 30 stage III/IV tumors (33%) were c-erbB-2-positive, whereas none of the 11 stage I/II tumors (0%) overexpressed the oncogene product (P = .04; Fisher exact test). The prognostic value of c-erbB-2 overexpression was not independent of stage (P = .7; Cox regression model).Conclusions: (1) The Laurén classification is an independent prognostic factor in adenocarcinoma of the esophagus and GEJ. (2) c-erbB-2 overexpression is limited to (areas of) intestinal-type tumors, indicating that intestinal- and diffuse-type tumors differ oncogenetically. (3) c-erbB-2 overexpression is associated with the stage of disease, indicating that it is a late event during tumor progression.WP, who was originally affiliated with the 2nd Department of General Surgery, Medical Academy (Lublin, Poland), is a fellow of the European Postgraduate Gastro-surgical School at the Academic Medical Center, University of Amsterdam (Amsterdam, The Netherlands).     

Low Grade Glandular Lesions of the Sinonasal Tract: A Focused Review

The sinonasal tract is a complex anatomic site with an exhaustive list of possible diagnoses. While most biopsies or resections encountered routinely consist of common diagnoses such as inflammatory polyps and papillomas, occasional cases are more difficult, and separating reactive or benign from malignancy can be challenging. One of the most poorly understood and daunting categories is low grade glandular or tubular proliferations, particularly on small biopsies. Possible diagnoses such as reactive lesions, respiratory epithelial adenomatoid hamartoma (REAH), seromucinous (glandular) hamartoma (SH) and low grade sinonasal adenocarcinomas (LGSNAC) must be entertained. REAH is composed of respiratory epithelial lined submucosal glands with variable connection to the surface and periglandular hyalinization. SH is a tubular proliferation reminiscent of normal serous glands which may be associated with REAH. LGSNAC is a diverse group of bland tubular and/or papillary tumors, which have a recurrence potential but an as yet uncertain potential for metastasis or mortality. The management for these lesions can be vastly different and conservative management is preferable, making this distinction more than academic. However, complicating this category are controversies surrounding their nature as reactive lesions versus neoplasms, the histologic and immunohistochemical overlap, and possible precursor relationships between some of them.     

Radiologic, pathologic and molecular attributes of two types of papillary renal adenocarcinomas.

OBJECTIVE: Most papillary renal tumors are not as aggressive as clear cell carcinomas and thus carry a better prognosis. However, several reports in the literature have demonstrated a subset of patients with papillary tumors that have a more aggressive biology and advanced stage at presentation. We compared several parameters of these subsets of renal tumors in an effort to characterize these lesions. PATIENTS AND METHODS: We reviewed 391 cases of nephrectomies that were performed for cancer over a 20-year period from four institutions. Of these, 41 were documented as papillary adenocarcinomas. We reviewed these cases with respect to stage at presentation, size, vascularity on (computerized tomography) CT scan, histology, and cytokeratin immunohistology. RESULTS: Thirty-two of the lesions presented in the fifth, sixth, seventh and eighth decades of life (Type I), while most of the remaining 9 tumors (Type II) presented in the fourth decade of life, and in more advanced stages. Tumor volumes ranged from 84 cm3 to 1660 cm3. Type I tumors had an average size of 515 cm3 and an enhancement on CT of 36 +/- 4 Hounsfield units, compared with Type II tumors which had an average size of 164 cm3 and an enhancement on CT of 92 +/- 8 Hounsfield units. Type II tumors also had a higher mean Fuhrman score of nuclear pleomorphism than Type I, and a greater expression of cytokeratin. CONCLUSIONS: We found that the more common Type I variant of papillary renal adenocarcinoma was less vascular on CT scan, larger in size, and had a lower amount of nuclear pleomorphism as well as decreased expression of cytokeratin 7. The more aggressive biological variant, Type II, presented in the earlier decades of life, with a smaller, but more vascular, cancer and had a greater nuclear pleomorphism. Nuclear pleomorphism still appears to have the best prognostic assessment. However, other molecular and genetic parameters of these tumors, as well as long-term survival data will be necessary to determine the significance of these findings.     

Heteromorphic grade of renal cell cancer

The present study demonstrates by means of histopathologic analysis that most of the renal adenocarcinomas are microscopically heterogeneous--named by authors as heteromorphic. This heteromorphism means the mixture of different cell types, histological patterns and fields of tumor with different nuclear atypia. 300 surgical specimens of renal cell cancer (RCC) were reclassified retrospectively. The histologic classification was as follows: 1. Nuclear atypia (nuclear grading according to Skinner); 2. Histological structure (compact, tubular, papillary, cystic); 3. Tumor cell types (clear, chromophobe, chromophilic basophilic, chromophilic eosinophilic). Homogeneous tumors consist of the three categories of this basic classifications. Heteromorphic tumors have combinations the three categories: different cell types (clear and granular) and/or histological elements (tubulo-papillary) and/or nuclear structure. Heteromorphism of RCC can be graded as: G-I: homogeneous structure (three patterns, one-one pattern of the three categories; G-II: 3 + 1 patterns.... G-III: 3 + 2 patterns.... G-IV: 3 + 3 or more patterns of the classification given above. This grading system is recommended for the heteromorphism of renal adenocarcinomas.     

Oncocytic adenocarcinoma of the stomach: parietal cell carcinoma

We report 10 cases of an unusual type of gastric adenocarcinoma that occurred in elderly patients 58-81 years of age. Histologically, the tumors were well to moderately differentiated tubular adenocarcinomas with very eosinophilic, finely granular cytoplasm. Immunohistochemical stains for antimitochondrial antibody were strongly positive. Ultrastructurally, the tumor cells had numerous mitochondria in their cytoplasm and occasional intracytoplasmic lumina with associated long microvilli. These histologic and ultrastructural features are similar to those of parietal cells in normal gastric fundic mucosa, but immunohistochemical staining of the tumors using four different antiparietal cell antibodies (anti-H(+)-K(+)-adenosine triphosphatase antibodies) was negative in all cases. Therefore, we think that these tumors were not parietal cell carcinomas but could be termed oncocytic adenocarcinomas, or adenocarcinomas with oncocytic differentiation. Previously reported cases of parietal cell carcinoma have been said to have a favorable prognosis, but it will be necessary to study a larger number of cases to determine the prognosis of oncocytic adenocarcinoma.     

Fluorodeoxyglucose-positron emission tomography in adenocarcinomas of the distal esophagus and cardia

Adenocarcinomas of the esophagogastric junction (AEG) are now recognized as a separate tumor entity with increasing incidence. The aim of the present study was to evaluate whether positron emission tomography (PET) using the glucose analog F-18-fluorodeoxyglucose (FDG) can be used for metabolic characterization of this tumor type. Fifty-two patients with histologically proven, locally advanced AEG (distal esophagus, type I: n = 31; cardia, type II: n = 21) were studied by FDG-PET. None of the tumors had been previously treated. Findings of endoscopy (growth type), endoluminal ultrasound (uT, uN), computed tomography (cN, cranio-caudal extent, tumor thickness), histological evaluation (Lauren classification, tumor grade), anatomical classification, and survival were correlated with the results of FDG-PET. There was no correlation between FDG uptake and clinical stage, grade, Lauren classification, or survival. All AEG I tumors were visualized by FDG-PET with high contrast, whereas FDG uptake by five AEG II tumors (24%) did not differ from background activity. In a quantitative analysis, mean FDG uptake of AEG I tumors was 1.6 times higher than that of AEG II tumors (p = 0.0005). PET can be used to visualize type I adenocarcinomas of the esophagogastric junction (AEG I). In AEG II tumors, however, the use of FDG-PET appears to be limited. The significantly higher FDG uptake of AEG I tumors compared to AEG II tumors suggests that these two tumor types differ in glucose utilization. This finding strengthens the hypothesis that AEG I and AEG II are two different tumor entities.     

Glandular Neoplasia of the Sinonasal Tract

Glandular lesions that cannot be diagnosed readily as salivary gland tumors occur uncommonly in the upper aerodigestive tract. They occur only with some frequency within the sinonasal tract. Well-characterized lesions at this site include the respiratory epithelial adenomatoid hamartoma, seromucinous hamartoma, and intestinal and non–intestinal-type adenocarcinomas. This article reviews the clinicopathologic features of these fascinating lesions.     

Intraductal papillary mucinous tumors of the pancreas

BACKGROUND: An increasing number of intraductal papillary mucinous tumors of the pancreas have been reported in recent years. The indolent character and favorable prognosis of this neoplasm have been described. METHODS: Intraductal papillary mucinous tumors were classified into main duct type (n = 8) and branch type (n = 28) according to the dominant location of the tumor. This single-institute study examined the clinicopathological features and outcome after surgical resection in patients with intraductal papillary mucinous tumors. RESULTS: The gender, age, tumor size, and prognosis were quite similar for the main duct type and branch type groups. Branch type tumors were more frequently located in the head of the pancreas than were main duct type tumors. Histological examination revealed that 88% of main duct type tumors were adenocarcinomas; however, only 46% of branch type tumors were adenocarcinomas. Five-year survival rates for the patients with all main duct type tumors (n = 8), main duct type adenocarcinoma (n = 7), all branch type tumors (n = 28), and branch duct adenocarcinoma (n = 13) were 100%, 100%, 90.6%, and 90.9%, respectively. CONCLUSIONS: Intraductal papillary mucinous tumors had a favorable prognosis after surgical treatment. A curative pancreatectomy should be indicated for this localized malignant tumor.     

Cytokeratin expression in adenocarcinomas of the esophagogastric junction: a comparative study of adenocarcinomas of the distal esophagus and of the proximal stomach

Adenocarcinomas of the esophagogastric junction form a heterogeneous group of tumors. We aimed to evaluate the value of the expression pattern of cytokeratins 7, 19, and 20 for their diagnosis and classification. A total of 85 cases of adenocarcinoma of the distal esophagus and 67 cases of adenocarcinoma of the proximal stomach, defined on strict topographical criteria, were investigated. About 90% of the adenocarcinomas of distal esophagus were positive for cytokeratins 7 and 19, in contrast to <45% of the adenocarcinomas of proximal stomach (p <0.01); 17.6% of the adenocarcinomas of the distal esophagus and 55.2% of the adenocarcinomas of the proximal stomach expressed cytokeratin 20 (p <0.01); and 74.1% of the adenocarcinomas of the distal esophagus and 23.8% of the adenocarcinomas of the proximal stomach had a CK7+/CK20- immunophenotype (p <0.01). In intestinal-type tumors a CK7+/CK20- immunophenotype had a sensitivity of 76.5%, a specificity of 84.5%, and a predictive positive value of 87.3% for the diagnosis of adenocarcinoma of the distal esophagus. Cytokeratin patterns are different in adenocarcinomas of the distal esophagus and in adenocarcinomas of the proximal stomach. A CK7+/CK20- pattern is highly suggestive of an esophageal origin and may be helpful for the correct classification of esophagogastric adenocarcinomas.